掲載種別：研究論文（学術雑誌）   出版者・発行元：BMJ  

Background

The efficacy of endovascular therapy (EVT) in patients with large ischemic core has been reported, but it remains unclear whether IV alteplase (IVT) has beneficial effects in addition to EVT in such patients. We evaluated the efficacy and safety of EVT with or without IVT.

Methods

The RESCUE-Japan LIMIT was an open-label, prospective, multicenter, randomized clinical trial to evaluate the efficacy and safety of EVT in stroke patients with large ischemic core, defined as Alberta Stroke Program Early CT Score (ASPECTS) 3–5. This subanalysis evaluated the differences in the effects of EVT with medical care (EVT group) compared with medical care alone (No-EVT group) between those who received IVT (IVT stratum) and those who did not (No-IVT stratum) before EVT.

Results

Among 202 enrolled patients, 147 (73%) did not receive IVT. In the No-IVT stratum, the modified Rankin Scale (mRS) score of 0–3 at 90 days was significantly higher in the EVT group than in the No-EVT group (31.1% vs 12.3%, OR 3.21 (95% CI 1.37 to 7.53)). In the IVT stratum, the mRS score of 0–3 was 30.8% in the EVT group and 13.8% in the No-EVT group (OR 2.78 (95% CI 0.72 to 10.7)) (interaction p=0.77). The incidence of symptomatic intracranial hemorrhage was not different between the two groups in the No-IVT stratum (OR 1.20 (95% CI 0.35 to 4.12)), but it was significantly higher in the EVT group than in the No-EVT group in the IVT stratum (11.5% vs 0%, p=0.03).

Conclusions

There was no difference in efficacy of EVT with or without IVT, while IVT before EVT might increase symptomatic intracranial hemorrhage in patients with large ischemic core.

Trial registration information

NCT03702413.

DOI： 10.1136/jnis-2023-020846

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掲載種別：研究論文（学術雑誌）   出版者・発行元：Elsevier BV  

DOI： 10.1016/j.jns.2023.120797

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記述言語：日本語   出版者・発行元：(一社)日本認知症学会  

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掲載種別：研究論文（学術雑誌）   出版者・発行元：Elsevier BV  

DOI： 10.1016/j.jns.2023.120810

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掲載種別：研究論文（学術雑誌）   出版者・発行元：Elsevier BV  

DOI： 10.1016/s0140-6736(23)01142-x

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記述言語：日本語   出版者・発行元：(一社)日本神経学会  

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記述言語：日本語   出版者・発行元：(一社)日本神経学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: To investigate whether ultra-early recombinant tissue-plasminogen activator (rt-PA) administration can improve patient outcomes on mechanical thrombectomy (MT) in patients with large vessel occlusion (LVO). METHODS: Participants comprised rt-PA-eligible 204 patients with internal carotid artery or middle cerebral artery occlusion in the SKIP trial, who were randomly assigned to receive mechanical thrombectomy alone or combined intravenous thrombolysis (rt-PA: alteplase at 0.6 mg/kg) plus mechanical thrombectomy. We assessed associations between onset-to-puncture time and onset-to-rt-PA administration time and frequency of favorable outcome at 90 days and any intracerebral hemorrhage (ICH) at 36 h after onset. RESULTS: As a cut-off onset-to-puncture time for favorable outcome, receiver operating characteristic curves defined 2.5 h (57% sensitivity, 62% specificity). For onset-to-puncture times ≤2.5 h and > 2.5 h, frequencies of favorable outcomes were 72% and 63% (p = 0.402) in patients with rt-PA therapy and 44% and 58% (p = 0.212) in patients without rt-PA therapy, respectively. In terms of onset-to-rt-PA administration time, frequencies of favorable outcomes among patients with ultra-early rt-PA administration at ≤100, >100 min after onset, and without rt-PA therapy with onset-to-puncture time ≤ 2.5 h, and with and without rt-PA therapy with onset-to-puncture time > 2.5 h were 84% and 64%, 63%, and 44% and 58%, respectively (p = 0.025). Frequencies of any ICH among those patients were 37% and 32%, 32%, and 63% and 40%, respectively (p = 0.006). CONCLUSION: Ultra-early rt-PA administration should improve patient outcomes on mechanical thrombectomy among patients with LVO. Relatively late rt-PA administration might increase the frequency of any ICH.

DOI： 10.1016/j.jns.2023.120772

PubMed

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掲載種別：研究論文（学術雑誌）   出版者・発行元：Frontiers Media SA  

Background

Cryptogenic stroke (CS) are heterogeneous in origin; however, most CS are embolic mechanism. Paroxysmal atrial fibrillation (AF) is suspected to be a major type of CS that leads to severe cerebral infarction without anticoagulant use. Therefore, the identification of AF is vital in patients with CS. However, patients are often unaware of AF because they have no symptoms, and AF may not be detected on an electrocardiogram (ECG) or Holter ECG on admission. After patients with stroke are treated in the acute phase, they are promptly transferred to a rehabilitation hospital for functional recovery. Once the patient is transferred to a hospital, a few attempts are made to detect AF. In addition, rehabilitation therapists are considered to have insufficient awareness of the possibility of undiagnosed AF.

Objective

This study aimed to increase the understanding of the importance of AF detection in patients with ischemic stroke among therapists in rehabilitation hospitals and to investigate whether regular pulse screening can aid in the detection of AF. If AF was detected, we determined the rate and timing of AF detection and identified the patient characteristics.

Methods

This multicenter prospective observational study aimed to detect AF in patients with non-cardiac stroke at rehabilitation hospitals. Therapists performed pulse checks before, during, and after rehabilitation. If arrhythmia or tachycardia was detected, an ECG was performed, and the physician checked for AF. If the patient complained of chest symptoms, electrocardiography (ECG) was performed to check for AF. We investigated the characteristics, laboratory data, cognitive status, complications, such as stroke recurrence, and functional outcomes of patients with AF.

Results

The study is in the enrollment phase. Recruitment began in September 2022 and will end in August 2023. Patients have provided written informed consent. The main results have been submitted for publication in your journal.

Conclusion

The findings of this study will help identify patients with AF in rehabilitation hospitals and improve awareness among therapists.

DOI： 10.3389/fneur.2023.1247020

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: The increased risk of intracranial hemorrhage with multiple passes in endovascular therapy (EVT) for large vessel occlusion with a large ischemic core is a concern. We explored the effect of the number of EVT passes on patients in a randomized clinical trial. METHODS: This post hoc study was the secondary analysis of RESCUE-Japan LIMIT, which was a randomized clinical trial comparing EVT and medical treatment alone for large vessel occlusion with large ischemic core. We grouped patients according to the number of passes with successful reperfusion (modified Thrombolysis in Cerebral Infarction score, ≥2b) in 1, 2, and 3 to 7 passes and failed reperfusion (modified Thrombolysis in Cerebral Infarction score, 0-2a) after any pass in the EVT group, and these groups were compared with medical treatment group. The primary outcome was modified Rankin Scale score of 0 to 3 at 90 days. Secondary outcomes were improvement in National Institutes of Health Stroke Scale score of ≥8 at 48 hours, mortality at 90 days, symptomatic intracranial hemorrhage, and any intracranial hemorrhage within 48 hours. RESULTS: The number of patients who received EVT with successful reperfusion after 1, 2, and 3 to 7 passes and failed reperfusion were 44, 23, 19, and 14, respectively, and 102 received medical treatment alone. The adjusted odds ratios (95% CIs) for the primary outcome relative to medical treatment were 5.52 (2.23-14.28) after 1 pass, 6.45 (2.22-19.30) after 2 passes, 1.03 (0.15-4.48) after 3 to 7 passes, and 1.17 (0.16-5.37) if reperfusion failed. The adjusted odds ratios (95% CIs) for any intracranial hemorrhage within 48 hours relative to medical treatment were 1.88 (0.90-3.93) after 1 pass, 5.14 (1.97-14.72) after 2 passes, 3.00 (1.09-8.58) after 3 to 7 passes, and 6.16 (1.87-24.27) if reperfusion failed. CONCLUSIONS: The successful reperfusion within 2 passes was associated with better clinical outcomes. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT03702413.

DOI： 10.1161/STROKEAHA.123.042552

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Diffusion-weighted imaging-Alberta Stroke Program Early Computed Tomography Score (DWI-ASPECTS) has been used to estimate infarct core volume in acute stroke. However, the same and indiscriminate score deduction for punctate or confluent DWI high-intensity lesion might lead to variation in performance. AIMS: To develop and evaluate a differential detailed DWI-ASPECTS method in comparison with the conventional DWI-ASPECTS in core infarct volume measurement and clinical outcome prediction. METHODS: We retrospectively recruited patients with acute ischemic stroke (AIS) treated with endovascular treatment between April 2013 and October 2019. In differential detailed DWI-ASPECTS, restricted diffusion lesion that was punctate or less than half of a cortical region (M1-M6) would not lead to subtraction of point. A favorable outcome was modified Rankin Scale score ⩽2 at 90 days after stroke onset. RESULTS: Among 298 AIS patients, mean age was 75 years (interquartile range (IQR) 67-82), and 194 patients (65%) were males. Mean infarct core volume was 11 mL (IQR 3-37). Overall, the score by detailed DWI-ASPECTS was significantly higher than conventional DWI-ASPECTS (8 (7-9) vs. 7 (5-9); P < 0.01). The detailed DWI-ASPECTS resulted in a higher correlation coefficient (r) for core infarct volume estimation than the conventional DWI-ASPECTS (r = 0.832 vs. 0.773; P < 0.01). Upon re-classification of those scored ⩽6 in conventional DWI-ASPECTS (n = 134) by detailed DWI-ASPECTS, the rate of favorable outcome in patients with detailed DWI-ASPECTS >6 was significantly higher than those with ⩽6 (29 (48%) vs. 14 (19%); P < 0.01). CONCLUSIONS: Detailed DWI-ASPECTS appeared to provide a more accurate infarct core volume measurement and clinical outcome correlation than conventional DWI-ASPECTS among AIS patients treated with endovascular therapy.

DOI： 10.1177/17474930231185468

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掲載種別：研究論文（学術雑誌）   出版者・発行元：Elsevier BV  

DOI： 10.1016/j.omtm.2023.07.005

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

INTRODUCTION: The aim of this study was to determine the safety and efficacy of intravenous (IV) alteplase at 0.6 mg/kg for patients with acute wake-up or unclear onset strokes in clinical practice. METHODS: This multicenter observational study enrolled acute ischemic stroke patients with last-known-well time >4.5 h who had mismatch between DWI and FLAIR and were treated with IV alteplase. The safety outcomes were symptomatic intracranial hemorrhage (sICH) after thrombolysis, all-cause deaths and all adverse events. The efficacy outcomes were favorable outcome defined as an mRS score of 0-1 or recovery to the same mRS score as the premorbid score, complete independence defined as an mRS score of 0-1 at 90 days, and change in NIHSS at 24 h from baseline. RESULTS: Sixty-six patients (35 females; mean age, 74±11 years; premorbid complete independence, 54 [82%]; median NIHSS on admission, 11) were enrolled at 15 hospitals. Two patients (3%) had sICH. Median NIHSS changed from 11 (IQR, 6.75-16.25) at baseline to 5 (3-12.25) at 24 h after alteplase initiation (change, -4.8±8.1). At discharge, 31 patients (47%) had favorable outcome and 29 (44%) had complete independence. None died within 90 days. Twenty-three (35%) also underwent mechanical thrombectomy (no sICH, NIHSS change of -8.5±7.3), of whom 11 (48%) were completely independent at discharge. CONCLUSIONS: In real-world clinical practice, IV alteplase for unclear onset stroke patients with DWI-FLAIR mismatch provided safe and efficacious outcomes comparable to those in previous trials. Additional mechanical thrombectomy was performed safely in them.

DOI： 10.1159/000530995

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記述言語：日本語   出版者・発行元：(株)へるす出版  

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記述言語：日本語   出版者・発行元：日本内科学会-関東地方会  

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記述言語：日本語   掲載種別：研究論文（学術雑誌）  

A 37-year-old man who had a low grade fever for 5 days admitted to our hospital due to disturbance of consciousness and seizure. Brain MRI showed abnormal hyperintensity in the bilateral temporal lobes, cortical and subcortical lesions on fluid-attenuated inversion recovery image. Treponemal and non-treponemal specific antibodies were positive in serum and cerebrospinal fluid, therefore he was diagnosed as having neurosyphilis. Treatment with intravenous penicillin G and metylpredonisolone improved his clinical symptons, imaging abnormalities and CSF findings. Patients of neurosyphilis with mesiotemporal encephalitis show common features such as young age, HIV-negative, subacute cognitive impairment and seizure, as seen in our case. Early diagnosis of neurosyphilis and appropriate treatment make clinical improvement, however the clinical diagnosis of neurosyphilis is sometime difficult because most patients present with disturbance of consciousness or seizure. The possibility of neurosyphilis should be considered when MRI results indicate temporal abnormalities.

DOI： 10.5692/clinicalneurol.cn-001811

PubMed

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

AIM: Studies investigating the relationship between pulse pressure (PP) and prognosis in acute ischemic stroke remain limited. Thus, in this study, we aim to determine whether changes in PP in the early phase of ischemic stroke are associated with neurological deterioration or stroke recurrence. METHODS: Patients who participated in the Acute Aspirin Plus Cilostazol Dual Therapy for Non-cardiogenic Stroke Patients Within 48 Hours of Symptom Onset (ADS) trial were included in this study. We then divided the patients into four groups (low-low, low-high, high-low, high-high) according to low or high PP both on admission and 24 h after admission. The threshold PP calculated by receiver operating characteristic curve analysis of PP on admission for neurological deterioration within 14 days and recurrent ischemic stroke/transient ischemic attack (TIA) within 3 months was 69 mmHg. RESULTS: Neurological deterioration within 14 days was observed in 118 patients (10.6%), whereas recurrent ischemic stroke/TIA within 3 months was noted in 34 patients (3.2%). Among these four groups, both neurological deterioration within 14 days (odds ratio [OR] 2.09, 95% confidence interval [CI] 1.12-3.91; p=0.0209) and recurrent ischemic stroke/TIA within 3 months (OR 4.80; 95% CI 1.62-14.86; p=0.0064) were significantly more frequent in the high-high group than in the low-low group as per the results of our multivariate analysis. In addition, neurological deterioration within 14 days was significantly higher in the high-low group than that in the low-low group (OR 2.70; 95% CI 1.44-5.05; p=0.0019). CONCLUSIONS: High PP during the acute phase of ischemic stroke appears to be associated with ischemic stroke recurrence and neurological deterioration, particularly if PP is elevated both on admission and 24 h later after admission.

DOI： 10.5551/jat.64079

PubMed

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Paroxysmal atrial fibrillation (AF) is a probable cause of cryptogenic stroke (CS), and its detection and treatment are important for the secondary prevention of stroke. Insertable cardiac monitors (ICMs) are clinically effective in screening for AF and are superior to conventional short-term cardiac monitoring. Japanese guidelines for determining clinical indications for ICMs in CS are stricter than those in Western countries. Differences between Japanese and Western guidelines may impact the detection rate and prediction of AF via ICMs in patients with CS. Available data on Japanese patients are limited to small retrospective studies. Furthermore, additional information about AF detection, including the number of episodes, cumulative episode duration, anticoagulation initiation (type and dose of regimen and time of initiation), rate of catheter ablation, role of atrial cardiomyopathy, and stroke recurrence (time of recurrence and cause of the recurrent event), was not provided in the vast majority of previously published studies. OBJECTIVE: In this study, we aim to identify the proportion and timing of AF detection and risk stratification criteria in patients with CS in real-world settings in Japan. METHODS: This is a multicenter, prospective, observational study that aims to use ICMs to evaluate the proportion, timing, and characteristics of AF detection in patients diagnosed with CS. We will investigate the first detection of AF within the initial 6, 12, and 24 months of follow-up after ICM implantation. Patient characteristics, laboratory data, atrial cardiomyopathy markers, serial magnetic resonance imaging findings at baseline, 6, 12, and 24 months after ICM implantation, electrocardiogram readings, transesophageal echocardiography findings, cognitive status, stroke recurrence, and functional outcomes will be compared between patients with AF and patients without AF. Furthermore, we will obtain additional information regarding the number of AF episodes, duration of cumulative AF episodes, and time of anticoagulation initiation. RESULTS: Study recruitment began in February 2020, and thus far, 213 patients have provided written informed consent and are currently in the follow-up phase. The last recruited participant (May 2021) will have completed the 24-month follow-up in May 2023. The main results are expected to be submitted for publication in 2023. CONCLUSIONS: The findings of this study will help identify AF markers and generate a risk scoring system with a novel and superior screening algorithm for occult AF detection while identifying candidates for ICM implantation and aiding the development of diagnostic criteria for CS in Japan. TRIAL REGISTRATION: UMIN Clinical Trial Registry UMIN000039809; https://tinyurl.com/3jaewe6a. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/39307.

DOI： 10.2196/39307

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND AND PURPOSE: Prior concomitant use of vitamin K antagonists (VKAs) and antiplatelet (AP) therapy increase the hematoma volume and mortality compared with VKA monotherapy in patients with intracranial hemorrhage (ICH). However, the prior concomitant use of non-vitamin K oral antagonists (NOACs) and AP has not been clarified. METHODS: We conducted a PASTA registry study, which was an observational, multicenter, registry of 1043 patients with stroke receiving oral anticoagulants (OACs) in Japan. In the present study, ICH from the PASTA registry was used to analyze the clinical characteristics including mortality among the four groups (NOAC, VKA, NOAC and AP, and VKA and AP) using univariate and multivariate analyses. RESULTS: Among the 216 patients with ICH, 118 (54.6%), 27 (12.5%), 55 (25.5%), 16 (7.4%) were taking NOAC monotherapy, NOAC and AP, VKA, and VKA and AP, respectively. In-hospital mortality rates were the highest in VKA and AP (31.3%) than in NOACs (11.9%), NOACs and AP (7.4%), and VKA (7.3%). Multivariate logistic regression analysis demonstrated that the concomitant use of VKA and AP (odds ratio [OR], 20.57; 95% confidence interval [CI], 1.75-241.75, p = 0.0162), initial National Institutes of Health Stroke Scale score (OR, 1.21; 95%CI, 1.10-1.37, p < 0.0001), hematoma volume (OR, 1.41; 95%CI, 1.10-1.90, p = 0.066), and systolic blood pressure (OR, 1.31; 95%CI, 1.00-1.75, p = 0.0422) were independently associated with in-hospital mortality. CONCLUSIONS: Although VKA in addition to AP therapy could increase the in-hospital mortality, NOAC and AP did not increase the hematoma volume, stroke severity, or mortality compared to NOAC monotherapy.

DOI： 10.1016/j.jns.2023.120643

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: The safety of intravenous recombinant tissue plasminogen activator (rtPA) and mechanical thrombectomy (MT) in patients treated with direct oral anticoagulants (DOACs) before stroke has not been fully investigated. Therefore, we aimed to investigate the safety of recanalization therapy in patients receiving DOACs. METHODS: We assessed data from a prospective multicenter registry of patients with stroke, including those with acute ischemic stroke (AIS) treated with rtPA and/or MT who were administered DOACs. We evaluated the safety of recanalization considering the DOACs dosage and interval between the last DOAC intake and recanalization. RESULTS: The final analysis included 108 patients (women, n = 54; median age, 81 years; DOAC overdose, n = 7; appropriate dose, n = 74; and inappropriate low dose, n = 27). The rate of any ICH differed significantly among overdose-, appropriate dose-, and inappropriate-low dose DOACs groups (71.4, 23.0, and 33.3%, respectively; P = 0.0121), whereas no significant difference was observed in respect of symptomatic ICH (P = 0.6895). Multivariate analysis showed that the National Institutes of Health Stroke Scale score on admission (odds ratio [OR]: 1.06, 95% confidence interval [CI]: 1.01-1.11; P = 0.0267) and overdose-DOAC (OR: 8.40, 95% CI: 1.24-56.88; P = 0.0291) were independently associated with any ICH. No relationship was observed between the timing of the last DOAC intake and occurrence of ICH in patients treated with rtPA and/or MT (all P > 0.05). CONCLUSION: Recanalization therapy during DOAC treatment may be safe in selected patients with AIS, if it is performed >4 h after the last DOAC intake and the patient is not overdosed with DOACs. REGISTRATION: https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000034958.

DOI： 10.1016/j.jns.2023.120639

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: The effectiveness of long-term dual antiplatelet therapy (DAPT) to prevent recurrent strokes in patients with lacunar stroke remains unclarified. Therefore, this study aimed to compare and to elucidate the safety and effectiveness of DAPT and single antiplatelet therapy (SAPT) in preventing recurrence in chronic lacunar stroke. METHODS: CSPS.com (Cilostazol Stroke Prevention Study for Antiplatelet Combination) was a prospective, multicenter, randomized controlled trial. In this prespecified subanalysis, 925 patients (mean age, 69.5 years; 69.4% men) with lacunar stroke were selected from 1884 patients with high-risk noncardioembolic stroke, enrolled in the CSPS.com trial after 8 to 180 days following stroke. Patients were randomly assigned to receive either SAPT or DAPT using cilostazol and were followed for 0.5 to 3.5 years. The primary efficacy outcome was the first recurrence of ischemic stroke. The safety outcomes were severe or life-threatening bleeding. RESULTS: The DAPT group receiving cilostazol and either aspirin or clopidogrel and SAPT group receiving aspirin or clopidogrel alone comprised 464 (50.2%) and 461 (49.8%) patients, respectively. Ischemic stroke occurred in 12 of 464 patients (1.84 per 100 patient-years) in the DAPT group and 31 of 461 patients (4.42 per 100 patient-years) in the SAPT group, during follow-up. After adjusting for multiple potential confounding factors, ischemic stroke risk was significantly lower in the DAPT group than in the SAPT group (hazard ratio, 0.43 [95% CI, 0.22-0.84]). The rate of severe or life-threatening hemorrhage did not differ significantly between the groups (2 patients [0.31 per 100 patient-years] versus 6 patients [0.86 per 100 patient-years] in the DAPT and SAPT groups, respectively; hazard ratio, 0.36 [95% CI, 0.07-1.81]). CONCLUSIONS: In patients with lacunar stroke, DAPT using cilostazol had significant benefits in reducing recurrent ischemic stroke incidence compared with SAPT without increasing the risk of severe or life-threatening bleeding. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT01995370. URL: https://www.umin.ac.jp/ctr; Unique identifier: UMIN000012180.

DOI： 10.1161/STROKEAHA.122.039900

PubMed

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記述言語：日本語   出版者・発行元：(一社)日本神経学会  

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記述言語：日本語   出版者・発行元：(一社)日本神経学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Objective In recent decades, living conditions have changed drastically. However, there are few data regarding the interaction between living conditions and the risk of ischemic stroke (IS) in young adults. The present study explored the association between living conditions or marital status and the risk factors, etiology, and outcome of IS in young adults. Methods We prospectively enrolled patients with incident IS who were 20-49 years old from 37 clinical stroke centers. We collected the demographic data, living conditions, marital status, vascular risk factors, disease etiology, treatment, and outcomes at discharge. A comparison group was established using the official statistics of Japan. We categorized patients into the two groups based on living conditions: solitary group and cohabiting group. Clinical characteristics were then compared between living conditions. Results In total, 303 patients were enrolled (224 men; median age at the onset: 44 years old). Significant factors associated with the incidence of IS were as follows: solitary status, body mass index >30 kg/m2, current smoking, heavy alcohol consumption, hypertension, diabetes mellitus, and dyslipidemia. Furthermore, in the solitary group, the proportions of men, unmarried individuals, and current smokers were significantly higher than in the cohabiting group. In addition, poor outcomes (modified Ranking Scale ≥ 4) of IS were more common in the solitary group than in the cohabiting group. Conclusion Our study showed that not only conventional vascular risk factors but also living conditions, especially living alone while unmarried, were independent risk factors for IS in young adults.

DOI： 10.2169/internalmedicine.0912-22

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

INTRODUCTION: Mechanical thrombectomy (MT) has been reported to be effective within 24 h after last known well (LKW) by the DAWN (DWI or CTP Assessment with Clinical Mismatch in the Triage of Wake-Up and Late Presenting Strokes Undergoing Neurointervention with Trevo) trial and within 16 h after LKW by the DEFUSE-3 (Endovascular Therapy Following Imaging Evaluation for Ischemic Stroke 3) trial. However, there have been few reports of MT more than 16 h after LKW, and the efficacy and safety of MT more than 24 h after LKW have not yet been demonstrated. We evaluated the efficacy and safety of MT more than 16 h after LKW. METHODS: Using data from the Nippon Medical School Hospital MT registry from April 2011 to August 2022, consecutive patients with anterior circulation large vessel occlusion (LVO) and prehospital modified Rankin scale (mRS) scores of 0-3 were enrolled. Patients were classified into the following three groups: early group (LKW &lt;6 h), middle group (LKW 6-16 h), and late group (LKW &gt;16 h). The clinical characteristics and outcomes were compared among these three groups. RESULTS: Among 778 patients in the MT registry, 624 were enrolled. The early group included 432 patients, the middle group included 123 patients, and the late group included 69 patients. The patients had a median age of 77 years (interquartile range, 68-83), and 359 were male (57.5%). The median prehospital mRS score was 1 (interquartile range, 1-1), median National Institutes of Health Stroke Scale score on admission was 17 (interquartile range, 10-23), and median Alberta Stroke Program Early CT Score was 10 (interquartile range, 8-10). Regarding safety and efficacy, the proportions of cases with successful reperfusion (modified Thrombolysis in Cerebral Infarction score of 2b-3; 85.4% vs. 92.7% vs. 88.7%; p = 0.47), symptomatic intracranial haemorrhage (6.4% vs. 5.7% vs. 7.2%; p = 0.99), mRS score ≤3 at 90 days (52.0% vs. 60.2% vs. 44.9%; p = 0.11), and mRS score of 6 at 90 days (11.3% vs. 10.6 vs. 8.7%; p = 0.37) were not significantly different between the three groups. CONCLUSION: Patients who received MT more than 16 h after LKW experienced the same safety and efficacy as those who received MT at 0-16 h after LKW. MT more than 16 h after LKW may be safe and effective for stroke patients with LVO.

DOI： 10.1159/000531153

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: There are a few accurate predictors of patient outcomes after mechanical thrombectomy (MT). OBJECTIVE: To investigate whether the National Institutes of Health Stroke Scale (NIHSS) score 24 hours after stroke onset could predict favorable outcomes at 90 days in patients with acute stroke treated with MT. METHODS: Patients from the SKIP study were enrolled in this study. Using receiver operating characteristic curves, the optimal cut-off NIHSS score 24 hours after stroke onset was calculated to distinguish between favorable (modified Rankin Scale score 0-2) and unfavorable (modified Rankin Scale score 3-6) outcomes at 90 days. These receiver operating characteristic curves were compared with those of previously reported predictors of favorable outcomes, such as the ΔNIHSS score (baseline NIHSS score-NIHSS score at 24 h), percent delta (ΔNIHSS score × 100/baseline NIHSS score), and early neurological improvement indices. RESULTS: A total of 177 patients (median age, 72 years; female, 65 [37%]) were enrolled, and 109 (61.9%) had favorable outcomes. The respective sensitivity, specificity, and area under the curve values for an NIHSS of 10 were 92.6%, 80.7%, and .906; a ΔNIHSS score of 7 were 70.6%, 76.1%, and .797; and percent delta of 48.3% were 85.3%, 80.7%, and .890. CONCLUSION: NIHSS score <10 at 24 hours after stroke onset is a strong predictor of favorable outcomes at 90 days in patients treated with MT.

DOI： 10.1227/neu.0000000000002139

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記述言語：日本語   出版者・発行元：(一社)日本脳循環代謝学会  

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記述言語：日本語   出版者・発行元：(一社)日本神経学会  

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記述言語：日本語   出版者・発行元：(一社)日本神経学会  

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記述言語：日本語   掲載種別：研究論文（学術雑誌）  

A 59-year-old woman presented with right hemiparesis and was transported from outside hospital. MRI revealed acute infarction and the left middle cerebral artery M2 occlusion. Intravenous infusion of recombinant tissue-type plasminogen activator, and mechanical thrombectomy (MT) were performed. The cause of cerebral infarction was diagnosed as Libman-Sacks endocarditis. She discharged without sequelae. After 10 months later, she presented with mild cognitive decline, and MRI showed new white matter lesion in left deep white matter. In magnetic resonance spectroscopy, the lesion showed an increased rate of choline/creatine, and a decreased rate of N-acetylaspartate/creatine, elevated lactate peak. When new higher brain dysfunction presented after recanalization by MT, it might be related to the delayed white matter lesion.

DOI： 10.5692/clinicalneurol.cn-001749

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記述言語：日本語   出版者・発行元：(一社)日本神経学会  

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記述言語：日本語   出版者・発行元：(一社)日本神経学会  

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記述言語：日本語   出版者・発行元：(一社)日本神経学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: We previously reported that dual antiplatelet therapy (DAPT) with cilostazol was superior to aspirin or clopidogrel for the prevention of recurrent stroke and vascular events in a subgroup analysis of intracranial arterial stenosis in the Cilostazol Stroke Prevention Study for Antiplatelet Combination (CSPS.com), a randomized controlled trial. AIMS: We conducted another subgroup analysis to investigate the benefit of DAPT with cilostazol in patients with extracranial arterial stenosis (ECAS) and those without arterial stenosis. METHODS: We compared the risk of recurrent ischemic stroke, vascular events, and major bleeding between DAPT with cilostazol plus aspirin or clopidogrel and aspirin or clopidogrel alone in patients with ischemic stroke between 8 and 180 days before starting trial treatment and ECAS or without arterial stenosis. RESULTS: The median follow-up period was 1.4 years. The risk of recurrent ischemic stroke (hazard ratio (HR): 1.04, 95% confidence interval (CI): 0.42-2.57) and vascular events (HR: 0.97, 95% CI: 0.42-2.24) did not differ between the two groups for the 253 patients with ECAS, whereas they were lower (HR: 0.36, 95% CI: 0.18-0.74 and HR: 0.47, 95% CI: 0.26-0.85, respectively) in the DAPT group for the 944 patients without arterial stenosis. The risk of major bleeding did not differ between the groups in patients with ECAS (HR: 0.58, 95% CI: 0.05-6.39) or without arterial stenosis (HR: 0.79, 95% CI: 0.27-2.26). CONCLUSION: DAPT with cilostazol might be beneficial for prevention of recurrent stroke and vascular events in patients without arterial stenosis but not in those with ECAS. DATA ACCESS STATEMENT: We will make the deidentified participant data from this research available to the scientific community with as few restrictions as feasible, while retaining exclusive use until the publication of major output.

DOI： 10.1177/17474930221112343

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND/AIMS: Early initiation of enteral nutrition (EN) is recommended for acute stroke patients, but it is time-consuming. Reducing EN administration time without increasing the frequency of complications is a worthwhile goal. We aimed to determine whether this goal was feasible. METHODS: Consecutive acute stroke patients with severe dysphagia within 72 h of hospital admission who received EN were retrospectively enrolled. Patients were classified into two groups (Rapid administration group: 100 mL/5 min on days 1-3 after stroke onset and 200 mL/30 min on days 4-7, Conventional administration group: 100 mL/h on days 1-3 and 200 mL/h on days 4-7). RESULTS: Among 118 consecutive acute stroke patients, 71 patients [median age, 77 (68-82) years; 37 (52%) males] were enrolled. The baseline clinical characteristics of the rapid administration group (45 patients) and the conventional administration group (26 patients) did not differ. The total duration of EN administration in the first week after stroke onset was significantly longer in the conventional vs. rapid administration group [21 (15-21) h vs. 6 (2-8) h, p < 0.01]. There were no significant differences in the frequency of diarrhea (42% vs. 42%, p = 1.00), vomiting (0% vs. 7%, p = 0.29), or pneumonia (15% vs. 7%, p = 0.41). There was also no difference in the percentage of patients with one or more complications (54% vs. 49%, p = 0.81). CONCLUSIONS: Rapid administration of EN is safe and has the potential to decrease the time required for EN feeding.

DOI： 10.1016/j.jns.2022.120270

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

INTRODUCTION: JTR-161 is a novel allogeneic human cell product consisting of dental pulp stem cells isolated from the extracted teeth of healthy adults. It is currently under development as a cell-based therapy for ischaemic stroke. The aim of this study is to evaluate the safety and efficacy of JTR-161 in patients with acute ischaemic stroke when given as a single intravenous administration within 48 hours of symptom onset. METHODS AND ANALYSIS: This is a first-in-human, randomised, double-blind, placebo-controlled, multicentre, phase 1/2 clinical trial to be conducted in Japan (from January 2019 to July 2021). Patients with a clinical diagnosis of anterior circulation ischaemic stroke with a National Institutes of Health Stroke Scale (NIHSS）score of 5-20 at baseline were enrolled. Patients previously treated with recombinant tissue-type plasminogen activator and/or endovascular thrombectomy were allowed to be enrolled. The study consists of three cohorts: cohorts 1 and 2 (each eight patients) and cohort 3 (60 patients). Subjects were randomly assigned to receive either JTR-161 or placebo in a 3:1 ratio in cohorts 1 and 2, and in a 1:1 ratio in cohort 3. The number of cells administered was increased sequentially from 1×108 (cohort 1) to 3 x 108 (cohort 2). In cohort 3, the higher tolerated dose among the two cohorts was administered. The primary endpoint is the proportion of patients who achieve an excellent outcome as defined by all of the following criteria at day 91 in cohort 3: modified Rankin Scale ≤1, NIHSS ≤1 and Barthel Index ≥95. ETHICS AND DISSEMINATION: The protocol and informed consent form were approved by the institutional review board at each participating study site. A manuscript with the results of the primary study will be published in a peer-reviewed journal. TRIAL REGISTRATION NUMBER: NCT04608838; JapicCTI-194570 and Clinical Trials. gov.

DOI： 10.1136/bmjopen-2021-054269

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

The pathophysiology of unilateral cortical fluid-attenuated inversion recovery (FLAIR)-hyperintense lesions in anti-myelin oligodendrocyte glycoprotein (MOG)-associated encephalitis with seizures (FLAMES) is unclear. A 26-year-old man was referred because of a seizure. FLAIR showed an increased signal intensity and swelling of the right frontal cortex. His symptoms and imaging abnormalities were improved after intravenous methylprednisolone therapy. MOG antibody was detected both in serum and cerebrospinal fluid (CSF). Therefore, the patient was diagnosed with FLAMES. Myelin basic protein (MBP) was elevated in CSF. The high MBP value in the CSF in the present case suggested that demyelination as well as inflammation can occur in some FLAMES patients.

DOI： 10.2169/internalmedicine.9439-22

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記述言語：日本語   掲載種別：研究論文（学術雑誌）  

The recent approval of prasugrel will expand the choice of medical treatment. Prasugrel, as a platelet inhibitor, was approved for the management of cardiovascular events (including stent thrombosis) in patients with acute coronary syndrome in 2009. In 2021, it was also approved for use in patients with ischemic stroke. However, there have been cases of patients showing resistance to medical treatment and, therefore, worsening symptoms. It is important to approach treatment while considering the next step. Physicians should be aware of medical treatment choices, including the use of antiplatelet drugs, as well as the appropriate timing to shift to surgical treatment when necessary. In this paper, clinical practice options and guidelines will be considered.

DOI： 10.11477/mf.1416202090

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記述言語：日本語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Intravenous immunoglobulin (IVIg) have been administrated for the long time in patients with several autoimmune neuromuscular diseases. Eczematous eruption has been described as IVIg-induced adverse effect. OBJECTIVE: The purpose of this study is to clarify the incidence and characteristic of IVIg-induced eczematous eruption in autoimmune neuromuscular disease. METHODS: We retrospectively collected the data from 92 patients with autoimmune neuromuscular diseases, including 35 patients with chronic inflammatory demyelinating polyneuropathy (CIDP), 8 patients with multifocal motor neuropathy (MMN), 25 patients with myositis, 15 patients with Guillain-Barré syndrome (GBS), and 9 patients with myasthenia gravis (MG), who have administrated IVIg in Yamaguchi University Hospital. RESULTS: There are 10 patients (6 CIDP/4 MMN), who had an eczematous skin reaction after IVIg infusion. The frequencies of IVIg-induced eczematous eruption were significantly higher in patients with multifocal acquired demyelinating sensory and motor (MADSAM) and MMN than in patients with GBS, myositis, and MG. In addition, corticosteroids or immunosuppressive drugs had been administrated before IVIg treatment more frequently in patients with myositis and MG than in those with MADSAM and MMN. CONCLUSION: MADSAM or MMN patients had more frequently IVIg-induced eczematous eruption than other autoimmune neuromuscular diseases. Pathophysiology of MADAM and MMN is considered to be cell-mediated immunity against the peripheral nerve and the accumulation of IgG in both epidermis and dermis of the hand after IVIg may induce the infiltration of inflammatory cells around the vessels in the skin, causing eczematous eruption in MADSAM and MMN.

DOI： 10.5692/clinicalneurol.cn-001681

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Endovascular therapy for acute ischemic stroke is generally avoided when the infarction is large, but the effect of endovascular therapy with medical care as compared with medical care alone for large strokes has not been well studied. METHODS: We conducted a multicenter, open-label, randomized clinical trial in Japan involving patients with occlusion of large cerebral vessels and sizable strokes on imaging, as indicated by an Alberta Stroke Program Early Computed Tomographic Score (ASPECTS) value of 3 to 5 (on a scale from 0 to 10, with lower values indicating larger infarction). Patients were randomly assigned in a 1:1 ratio to receive endovascular therapy with medical care or medical care alone within 6 hours after they were last known to be well or within 24 hours if there was no early change on fluid-attenuated inversion recovery images. Alteplase (0.6 mg per kilogram of body weight) was used when appropriate in both groups. The primary outcome was a modified Rankin scale score of 0 to 3 (on a scale from 0 to 6, with higher scores indicating greater disability) at 90 days. Secondary outcomes included a shift across the range of modified Rankin scale scores toward a better outcome at 90 days and an improvement of at least 8 points in the National Institutes of Health Stroke Scale (NIHSS) score (range, 0 to 42, with higher scores indicating greater deficit) at 48 hours. RESULTS: A total of 203 patients underwent randomization; 101 patients were assigned to the endovascular-therapy group and 102 to the medical-care group. Approximately 27% of patients in each group received alteplase. The percentage of patients with a modified Rankin scale score of 0 to 3 at 90 days was 31.0% in the endovascular-therapy group and 12.7% in the medical-care group (relative risk, 2.43; 95% confidence interval [CI], 1.35 to 4.37; P = 0.002). The ordinal shift across the range of modified Rankin scale scores generally favored endovascular therapy. An improvement of at least 8 points on the NIHSS score at 48 hours was observed in 31.0% of the patients in the endovascular-therapy group and 8.8% of those in the medical-care group (relative risk, 3.51; 95% CI, 1.76 to 7.00), and any intracranial hemorrhage occurred in 58.0% and 31.4%, respectively (P<0.001). CONCLUSIONS: In a trial conducted in Japan, patients with large cerebral infarctions had better functional outcomes with endovascular therapy than with medical care alone but had more intracranial hemorrhages. (Funded by Mihara Cerebrovascular Disorder Research Promotion Fund and the Japanese Society for Neuroendovascular Therapy; RESCUE-Japan LIMIT ClinicalTrials.gov number, NCT03702413.).

DOI： 10.1056/NEJMoa2118191

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記述言語：日本語   出版者・発行元：(一社)日本神経学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Regenerative medicine aims to restore human functions by regenerating organs and tissues using stem cells or living tissues for the treatment of organ and tissue defects or dysfunction. Clinical trials investigating the treatment of cerebral infarction using mesenchymal stem cells, a type of somatic stem cell therapy, are underway. The development and production of regenerative medicines using somatic stem cells is expected to contribute to the treatment of cerebral infarction, a central nervous system disease for which there is no effective treatment. Numerous experimental studies have shown that cellular therapy, including the use of human dental pulp stem cells, is an attractive strategy for patients with ischemic brain injury. This review describes the basic research, therapeutic mechanism, clinical trials, and future prospects for dental pulp stem cell therapy, which is being investigated in Japan in first-in-human clinical trials for the treatment of patients with acute cerebral ischemia.

DOI： 10.3390/biomedicines10040737

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND AND PURPOSE: Prescribing under-dose direct oral anticoagulants (DOACs) for non-valvular atrial fibrillation (NVAF) is alerted to increase cardiovascular events or death. However, the association between dose selection of DOACs and the clinical course remains unclear. This study aimed to propose a novel criterion for selecting the DOAC dose and investigate clinical characteristics of ischemic stroke (IS) under this criterion. METHODS: We assessed the pooled prospective multicenter registry data of stroke patients taking anticoagulant agents, including IS patients with NVAF and prior DOAC usage. The recommended dose according to the reduction criteria of each DOAC and the selected dose were identified for each patient, and patients were categorized into four groups: no alternative low-dose, selecting low-dose appropriately with all DOACs applicable for reduction criteria; selected low-dose, selecting low-dose appropriately or inappropriately despite at least one DOAC inapplicable for reduction criteria; selected standard-dose, appropriate standard-dose use; and absolute over-dose, inappropriate standard-dose regardless of criteria. We investigated the effects of dose selection of DOACs on short-term poor functional outcomes. RESULTS: 322 patients were included in the analysis. The prevalence of no alternative low-dose, selected low-dose, selected standard-dose, and absolute over-dose was 74 (23%), 144 (45%), 89 (27%), and 15 (5%), respectively. Multivariable analysis found that the selected low-dose group showed significantly poorer functional outcomes than the selected standard-dose group only in patients without renal dysfunction (OR, 2.60; 95% CI, 1.17-6.00; P = 0.0186). CONCLUSIONS: Selecting a low dose DOAC might be associated with poor functional outcomes in patients without renal dysfunction.

DOI： 10.1016/j.jns.2022.120163

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Atrial fibrillation (AF) includes paroxysmal and sustained (persistent or permanent) AF, and both forms are considered risk factors for ischemic stroke. This study aimed to investigate the differences in stroke severity at admission between patients with paroxysmal AF and sustained AF when treated with direct oral anticoagulants (DOACs). METHODS: Using data from DOAC-treated 300 nonvalvular patients with AF and acute anterior circulation stroke who were registered in the Multicenter Prospective Analysis of Stroke Patients Taking Oral Anticoagulants study, patients were divided into two groups, namely, paroxysmal AF and sustained AF. We compared the clinical characteristics between the two groups and determined the effect of these two types of AF on stroke severity on admission. RESULTS: Of 300 patients, 246 (males, n = 149; median age, 80 years) and 54 (males, n = 32; median age, 78 years) were assigned to the sustained AF and paroxysmal AF groups, respectively. The sustained AF group had a higher proportion of severe stroke (National Institutes of Health Stroke Scale score, >20) on admission (22.0% vs. 5.7%, p = 0.006) and internal carotid artery occlusion (11.4% vs. 1.9%, p = 0.03) compared to the paroxysmal AF group. Multivariate analysis showed that sustained AF was independently associated with severe stroke on admission (odds ratio 4.31, 95% confidence interval 1.24-15.0, p = 0.02). CONCLUSIONS: Sustained AF was associated with a higher severity of stroke accompanied with major vessel occlusion than paroxysmal AF, even prior to DOACs treatment. Registration https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000034958.

DOI： 10.1016/j.jns.2022.120172

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Objective Limited data exist regarding the comparative detailed clinical characteristics of patients with ischemic stroke (IS)/transient ischemic attack (TIA) and intracerebral hemorrhage (ICH) receiving oral anticoagulants (OACs). Methods The prospective analysis of stroke patients taking oral anticoagulants (PASTA) registry, a multicenter registry of 1,043 stroke patients receiving OACs [vitamin K antagonists (VKAs) or non-vitamin K antagonist oral anticoagulant (NOACs)] across 25 medical institutions throughout Japan, was used. Univariate and multivariable analyses were used to analyze differences in clinical characteristics between IS/TIA and ICH patients with atrial fibrillation (AF) who were registered in the PASTA registry. Results There was no significant differences in cardiovascular risk factors, such as hypertension, diabetes mellitus, dyslipidemia, smoking, or alcohol consumption (all p>0.05), between IS/TIA and ICH among both NOAC and VKA users. Cerebral microbleeds (CMBs) [odds ratio (OR), 4.77; p<0.0001] were independently associated with ICH, and high brain natriuretic peptide/N-terminal pro B-type natriuretic peptide levels (OR, 1.89; p=0.0390) were independently associated with IS/TIA among NOAC users. A history of ICH (OR, 13.59; p=0.0279) and the high prothrombin time-international normalized ratio (PT-INR) (OR, 1.17; p<0.0001) were independently associated with ICH, and a history of IS/TIA (OR, 3.37; 95% CI, 1.34-8.49; p=0.0101) and high D-dimer levels (OR, 2.47; 95% CI, 1.05-5.82; p=0.0377) were independently associated with IS/TIA among VKA users. Conclusion The presence of CMBs, a history of stroke, natriuretic peptide and D-dimer levels, and PT-INR may be useful for risk stratification of either IS/TIA or ICH development in patients with AF receiving OACs.

DOI： 10.2169/internalmedicine.8113-21

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Endovascular therapy is strongly recommended for acute cerebral large vessel occlusion (LVO) with an Alberta stroke program early computed tomography score (ASPECTS) ≥6 due to occlusion of the internal carotid artery or M1 segment of the middle cerebral artery. However, the effect of endovascular therapy for patients with a large ischemic core with an ASPECTS ≤5 (0-5) was not established. A multicenter, randomized, open-label, parallel-group trial was conducted to investigate the superiority of endovascular therapy over medical therapy without endovascular therapy for a large ischemic core with ASPECTS (3-5). Patients were randomly assigned to receive endovascular therapy or without endovascular therapy at a ratio of 1:1. The primary outcome was a moderate functional outcome, defined as a modified Rankin scale (mRS; scores ranging from 0 [no symptoms] to 6 [death]) ≤3 after 90 days. The secondary outcomes were defined as ordinal mRS, good functional outcome (mRS ≤2), excellent functional outcome (mRS ≤1), mRS shift analysis after 90 days, and early improvement of neurological findings at 48 hours. A total sample size of 200 was estimated to provide a power of 0.9 with a two-sided alpha of 0.05, for the primary outcome, considering a 15% dropout rate. This randomized clinical trial reported the applicability of endovascular therapy in patients with acute cerebral LVO with a large ischemic core.

DOI： 10.2176/nmc.rc.2021-0311

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

AIM: A previous randomized study showed that dual antiplatelet therapy (DAPT) with aspirin and cilostazol is not superior to aspirin monotherapy for patients with acute non-cardioembolic stroke; however, the reason for this remains uncertain. We focused on the unusual side effects of cilostazol, namely, tachycardia changes, and validated their influence on patients with acute non-cardioembolic stroke. METHODS: This post-hoc study extracted data from the acute aspirin plus cilostazol dual therapy study (ADS) registry, a multicenter, prospective, randomized, open-label trial. Patients were randomly allocated to the dual group (aspirin plus cilostazol) and the aspirin monotherapy group (aspirin alone). Tachycardia changes were defined as ≥ 5% heart rate increase at 48 h after admission compared with that at admission. Baseline data and outcomes were validated with four divided groups: aspirin-non-tachycardia changes (AN), aspirin-tachycardia changes (AT), dual-non-tachycardia changes (DN), and dual-tachycardia changes (DT). RESULTS: Finally, 1,188 patients were analyzed in this ADS post-hoc analysis (aspirin monotherapy group, 594; dual group, 594). The proportion of change in tachycardia was 19.2% in the aspirin monotherapy group and 38.2% in the dual group (p＜0.001＊＊＊). Although the recurrences of symptomatic stroke and transient ischemic attack were not significantly different, the neurological deterioration was significantly different among the AN, AT, DN, and DT groups (p＜0.05＊). CONCLUSIONS: Tachycardia changes increase neurological deterioration even in patients with non-cardioembolic acute stroke. DAPT consisting of aspirin and cilostazol increases the proportion of tachycardia changes and is not superior to aspirin monotherapy.

DOI： 10.5551/jat.63409

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND AND OBJECTIVES: Long-term treatment with the combination of cilostazol with aspirin or clopidogrel showed a lower risk of stroke recurrence compared to aspirin or clopidogrel alone after high-risk noncardioembolic ischemic stroke in a randomized trial. We aimed to determine whether the effect of the dual medication compared to monotherapy on risk of recurrent ischemic stroke differs according to timing of starting medication after stroke onset. METHODS: In a subanalysis of the randomized controlled trial, patients between 8 and 180 days after stroke onset were randomly assigned to receive aspirin or clopidogrel alone or a combination of cilostazol with aspirin or clopidogrel. They were divided into 3 groups according to the timing of starting trial treatment: between 8 and 14 days after stroke onset (8-14 days group), between 15 and 28 days after stroke onset (15-28 days group), and between 29 and 180 days after stroke onset (29-180 days group). The primary efficacy outcome was the first recurrence of ischemic stroke. Safety outcomes included severe or life-threatening bleeding. RESULTS: Of 1,879 patients, 498 belonged to the 8-14 days group, 467 to the 15-28 days group, and 914 to the 29-180 days group. There was a significant treatment-by-subgroup interaction for the recurrence of ischemic stroke between trial treatment and trichotomized groups. The recurrence of ischemic stroke was less common with dual therapy than with monotherapy in the 15-28 days group (annualized rate 1.5% vs 4.9%, respectively; adjusted hazard ratio 0.34 [95% CI 0.12-0.95]) and the 29-180 days group (1.9% vs 4.4%, respectively; 0.27 [0.12-0.63]) and similarly common in the 8-14 days group (4.5% for both; 1.02 [0.51-2.04]). Severe or life-threatening bleeding occurred similarly between patients on dual therapy and those on monotherapy in any of the trichotomized groups (crude hazard ratio 0.22 [95% CI 0.03-1.88] in the 8-14 days group, 1.07 [0.15-7.60] in the 15-28 days group, and 0.76 [0.24-2.39] in the 29-180 days group). DISCUSSION: Long-term dual antiplatelet therapy using cilostazol starting 15-180 days after stroke onset, compared to therapy started 8-14 days after onset, was more effective for secondary stroke prevention than monotherapy without increasing hemorrhage risk. TRIAL REGISTRATION INFORMATION: ClinicalTrials.gov NCT01995370; UMIN Clinical Trials Registry 000012180. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that for patients with acute noncardioembolic stroke taking either aspirin or clopidogrel, the addition of cilostazol 15-180 days after stroke onset decreases the risk of recurrent ischemic stroke.

DOI： 10.1212/WNL.0000000000200064

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Most trials comparing endovascular treatment (EVT) alone versus intravenous thrombolysis with alteplase (IVT) + EVT in directly admitted patients with a stroke are non-inferiority trials. However, the margin based on the level of uncertainty regarding non-inferiority of the experimental treatment that clinicians are willing to accept to incorporate EVT alone into clinical practice remains unknown. OBJECTIVE: To characterize what experienced stroke clinicians would consider an acceptable level of uncertainty for hypothetical decisions on whether to administer IVT or not before EVT in patients admitted directly to EVT-capable centers. METHODS: A web-based, structured survey was distributed to a cross-section of 600 academic neurologists/neurointerventionalists. For this purpose, a response framework for a hypothetical trial comparing IVT+EVT (standard of care) with EVT alone (experimental arm) was designed. In this trial, a similar proportion of patients in each arm achieved functional independence at 90 days. Invited physicians were asked at what level of certainty they would feel comfortable skipping IVT in clinical practice, considering these hypothetical trial results. RESULTS: There were 180 respondents (response rate: 30%) and 165 with complete answers. The median chosen acceptable uncertainty suggesting reasonable comparability between both treatments was an absolute difference in the rate of day 90 functional independence of 3% (mode 5%, IQR 1-5%), with higher chosen margins observed in interventionalists (aOR 2.20, 95% CI 1.06 to 4.67). CONCLUSION: Physicians would generally feel comfortable skipping IVT before EVT at different certainty thresholds. Most physicians would treat with EVT alone if randomized trial data suggested that the number of patients achieving functional independence at 90 days was similar between the two groups, and one could be sufficiently sure that no more than 3 out of 100 patients would not achieve functional independence at 90 days due to skipping IVT.

DOI： 10.1136/neurintsurg-2022-018665

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

PURPOSE: To investigate the effect of alteplase, either combined with stent-retriever thrombectomy or a direct aspiration first pass technique (ADAPT), in patients with large-vessel occlusion stroke. METHODS: This was a retrospective post hoc analysis of data from The Direct Mechanical Thrombectomy in Acute LVO Stroke (SKIP) study. Patients were divided into two groups according to the first-line thrombectomy technique: stent-retriever and ADAPT. Each group was further divided into two subgroups, namely MT and MT + alteplase. The procedural outcomes, such as first pass effect (FPE) ratio and number of passes, were evaluated. The clinical outcomes included mRS score at 3 months. RESULTS: A total of 180 patients were included (116 in the stent-retriever group and 64 in the ADAPT group). No interaction was detected between the first-line technique and alteplase administration. In the stent-retriever group, after adjusting for factors associated with FPE, the adjusted odds ratio (95% confidence interval) of FPE of the MT + alteplase subgroup versus the MT subgroup was 3.57 (1.5-8.48) and in the ADAPT group it was 1.35 (0.37-4.91). With alteplase, the number of passes decreased with adjusted odds ratios of 0.59 (0.37-0.93) in the stent-retriever group but not in the ADAPT group. In both first-line technique groups, clinical outcomes did not differ between subgroups. CONCLUSION: In the SKIP study, alteplase administration was associated with increased FPE when combined with stent-retriever thrombectomy, but not with ADAPT. We found no differences in the clinical outcomes.

DOI： 10.1007/s00062-021-01085-3

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

AIM: This study aimed to assess the potential effect of prior antithrombotic medication for thrombolysis in an unknown onset stroke. METHODS: This was a predefined sub-analysis of the THAWS trial. Stroke patients with a time last known well ＞4.5 h who had a DWI-fluid-attenuated inversion recovery mismatch were randomly assigned (1:1) to receive alteplase at 0.6 mg/kg (alteplase group) or standard medical treatment (control group). Patients were dichotomized by prior antithrombotic medication. RESULTS: Of 126 patients (intention-to-treat population), 40 took antithrombotic medication (24 with antiplatelets alone, 13 with anticoagulants alone, and 3 with both), and the remaining 86 did not before stroke onset. Of these, 17 and 52 patients, respectively, received alteplase, and 23 and 34, respectively, had standard medical treatment. Antithrombotic therapy was initiated within 24 h after randomization less frequently in the alteplase group (12% vs. 86%, p＜0.01). Both any intracranial hemorrhage within 22-36 h (26% vs. 14%) and a modified Rankin Scale score of 0-1 at 90 days (good outcome) (47% vs. 48%) were comparable between the two groups. A good outcome was more common in the alteplase group than in the control group in patients with prior antithrombotic medication [relative risk (RR) 2.25, 95% confidence interval (CI) 1.02-4.99], but it tended to be less common in the alteplase group in those without (RR 0.69, 95% CI 0.46-1.03) (p＜0.01 for interaction). The frequency of any intracranial hemorrhage did not significantly differ between the two groups in any patients dichotomized by prior antithrombotic medication. CONCLUSION: Alteplase appears more beneficial in patients with prior antithrombotic medication.

DOI： 10.5551/jat.63337

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Increasing evidence suggests improved time metrics leading to better clinical outcomes when stroke patients with suspected large vessel occlusion (LVO) are transferred directly to the angiography suite (DTAS) compared with cross-sectional imaging followed by transfer to the angiography suite. We performed a systematic review and meta-analysis on the efficacy and safety of DTAS approaches. METHODS: We searched Embase, Medline, Scopus, and clinicaltrials.gov for studies comparing outcomes of DTAS and conventional triage. Eligible studies were assessed for risk of bias. We performed a random-effects meta-analysis on the differences of median door-to-groin and door-to-reperfusion times between intervention and control group. Secondary outcomes included good outcome at 90 days (modified Rankin Scale ⩽ 2) rate of symptomatic intracranial hemorrhage (sICH) and mortality within 90 days. RESULTS: Eight studies (one randomized, one cluster-randomized trial and six observational studies) with 1938 patients were included. Door-to-groin and door-to-reperfusion times in the intervention group were on median 29.0 min [95% confidence interval (CI): 14.3-43.6; p < 0.001] and 32.1 min (95% CI: 15.1-49.1; p < 0.001) shorter compared with controls. Prespecified subgroup analyses for transfer (n = 1753) and mothership patients (n = 185) showed similar reductions of the door-to-groin and door-to-reperfusion times in response to the intervention. The odds of good outcome did not differ significantly between both groups but were numerically higher in the intervention group (odds ratio: 1.38, 95% CI: 0.97-1.95; p = 0.07). There was no significant difference for mortality and sICH between the groups. CONCLUSION: DTAS approaches for the triage of suspected LVO patients led to a significant reduction in door-to-groin and door-to-reperfusion times but an effect on functional outcome was not detected. The subgroup analysis showed similar results for transfer and mothership patients.Registration: This study was registered in PROSPERO (CRD42020213621).

DOI： 10.1177/17562864221078177

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Objectives: Patients with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) show various clinical symptoms, including migraine, recurrent stroke, and cognitive impairment. We investigated the associations between magnetic resonance imaging (MRI) markers of small vessel disease and neuropsychological tests and identified the MRI characteristics for predicting cognitive impairment in patients with CADASIL. Methods: Subjects included 60 CADASIL patients diagnosed with genetic tests and registered in the Japanese CADASIL REDCap database between June 2016 and December 2020. Patient information including clinical data, modified Rankin Scale (mRS); MRI findings of small vessel disease including periventricular and deep white matter lesions (WML), lacunar infarcts, and cerebral microbleeds (CMBs); and neuropsychological tests, including the Japanese version of the Mini-Mental State Examination (MMSE), the Japanese version of the Montreal Cognitive Assessment (MoCA-J), and the Frontal Assessment Battery (FAB), were evaluated. Results: Data from 44 CADASIL patients were eligible for this study, compared between patients with and without dementia. Regarding the neuroimaging findings, the Fazekas score of periventricular and deep WML was higher in patients with dementia (periventricular, p = 0.003; deep, p = 0.009). The number of lacunar infarcts was higher in patients with dementia (p = 0.001). The standardized partial regression coefficient (SPRC) in MoCA-J was 0.826 (95% CI, 0.723-0.942; p = 0.005) for the number of CMBs. The SPRC in MMSE was 0.826 (95% CI, 0.719-0.949; p = 0.007) for the number of CMBs. The SPRC for FAB decreased significantly to 0.728 (95% CI, 0.551-0.960; p = 0.024) for the number of lacunar infarcts. Receiver operating characteristic (ROC) curves for dementia showed that in the number of lacunar infarcts, a cut-off score of 5.5 showed 90.9% sensitivity and 61.1% specificity. For the number of CMBs, a cut-off score of 18.5 showed 45.5% sensitivity and 100% specificity. Conclusion: The characteristic MRI findings were that CADASIL patients with dementia had severe WML, both periventricular and deep, and a larger number of lacunar infarcts than those without dementia. The risk of dementia may be associated with ≥ 6 lacunar infarcts, ≥19 CMBs, or a Fazekas scale score of 3 in periventricular and deep WML.

DOI： 10.3389/fnagi.2022.876437

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Headache is frequently reported as a neurological manifestation of myeloproliferative neoplasms (MPNs), including polycythemia vera and essential thrombocythaemia. This study sought to clarify the clinical characteristics and response to treatment of headaches in patients with MPNs. METHODS: We prospectively studied 137 patients with MPNs. The following information was gathered to assess the features of headache at baseline and at follow-up (>6 months): (1) average duration of headache attacks, (2) number of headache days per month, (3) numerical rating scale (NRS), (4) Headache Impact Test-6 (HIT-6), and (5) Migraine Disability Assessment (MIDAS). We compared those parameters for headaches between the baseline and follow-up interviews according to the management. RESULTS: Thirty-seven (27.0%) patients had headache. The prevalence of headaches gradually decreased with increasing age (Age ≤ 49 years: 61.0%, 50-59 years: 38.5%, 60-69 years: 17.2%, 70-79 years: 5.1%, and ≥80 years: 0.0%, P < 0.001). Multiple logistic regression analysis showed that younger age, but not platelet counts or the JAK2 V617F mutation, was independently associated with headaches (Odds Ratios 2.004, 95% confidence intervals 1.293-3.108, P = 0.002). Scintillating scotomas were present in 22 (59.5%) of 37 patients with headaches, while four patients developed sudden headaches that lasted for only 0-10 min. Follow-up interviews were available for 31 (83.8%) of 37 patients with headaches. Twenty-one (67.7%) patients were treated with low-dose aspirin (100 mg once daily) [low-dose aspirin alone: n = 9; combined cytoreductive therapy: n = 12] for headache management. All parameters for headache [average duration of headache attacks, number of headache days per month, NRS score, HIT-6 score, and MIDAS score (all P < 0.001)] were significantly improved at follow-up in patients taking low-dose aspirin. However, there were no significant differences in these parameters of headaches in patients who did not receive low-dose aspirin. CONCLUSION: Headaches is common in patients with MPNs, particularly in younger patients. MPN-related headaches may be managed by using low-dose aspirin and controlling MPNs.

DOI： 10.3389/fneur.2022.1051093

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Ischemic stroke is a very rare etiology in cases of isolated trochlear nerve palsy, and no reports of ipsilateral trochlear nerve palsy caused by unilateral stroke have so far been published. However, we now report a case of isolated trochlear nerve palsy due to ipsilateral dorsal small midbrain infarction in a 70-year-old woman who presented with acute onset of diplopia. There were no other clinical manifestations, but brain magnetic resonance imaging revealed a small ischemic lesion in the right dorsal midbrain, showing that isolated trochlear nerve palsy can be caused by stroke.

DOI： 10.1272/jnms.JNMS.2021_88-515

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記述言語：日本語   出版者・発行元：(株)へるす出版  

当院に入院した虚血性椎骨脳底動脈解離症例のうち、脳梗塞を発症し、急性期に脳血管内治療としてステント留置術を行った4例(男性3例、女性1例、平均年齢34.3歳)について検討した。その結果、解離部位は両側2例、右側1例、左側1例であった。ステント留置術後から3ヵ月のmRSはmRS 0が2例、mRS 1が2例と、全例で転帰良好であった。

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

In patients who undergo mechanical thrombectomy for intracranial large vessel occlusion, the occluded site is sometimes distal to the site shown in the initial vascular imaging. We investigated the factors related to the change in the occluded site between the sequential imagings. The 203 patients in the SKIP study were reviewed retrospectively. Magnetic resonance angiography (MRA) or computed tomography angiography (CTA) was used to assess the occluded site. The occluded site shown in the cerebral angiography appeared to be distal to the occluded site shown in the initial vascular imaging in 55 patients (group A). The location of the occluded site in the remaining 148 patients did not change between the sequential imagings (group B). MRA was used more often than CTA in group A (54 MRA, 1 CTA; P <0.01). Patients with middle cerebral artery (M1) occlusion were more likely to show change of the occluded site than patients with internal carotid artery (ICA) occlusion (M1: 38%, ICA: 9%; P <0.01). The number of patients who received intravenous recombinant tissue plasminogen activator did not differ between the two groups (group A: 54%, group B: 49%; P = 0.5). In patients with acute intracranial large vessel occlusion who require mechanical thrombectomy, physicians should be aware that the location of the thrombus may be distal to the occluded site shown in the initial vascular imaging, particularly in patients with M1 occlusion shown by MRA.

DOI： 10.2176/nmc.oa.2021-0137

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記述言語：日本語   出版者・発行元：(NPO)日本脳神経血管内治療学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Background and Purpose: Although dual antiplatelet therapy (DAPT) with aspirin and clopidogrel reduces the recurrence of ischemic stroke while significantly increasing the bleeding events compared with monotherapy, the CSPS.com trial (Cilostazol Stroke Prevention Study combination) showed that DAPT using cilostazol was more effective without the bleeding risk. In the CSPS.com trial, aspirin or clopidogrel was used as the underlying antiplatelet drug. The effectiveness and safety of each combination were examined and clarified. Methods: In the CSPS.com trial, a multicenter, open-label, randomized controlled study, patients with high-risk, noncardioembolic ischemic stroke 8 to 180 days after onset treated with aspirin or clopidogrel alone at the discretion of the physician in charge were recruited. Patients were randomly assigned to receive either monotherapy or DAPT using cilostazol and followed for 0.5 to 3.5 years. The primary efficacy outcome was first recurrence of ischemic stroke. The safety outcome was severe or life-threatening bleeding. The analysis was based on the underlying antiplatelet agents. Results: A total of 763 patients taking aspirin and 1116 taking clopidogrel were included in the intention-to-treat analysis. Although the clopidogrel group had more risk factors than the aspirin group, the primary efficacy outcome and safety outcome did not differ significantly between the 2 groups. In the aspirin group, the primary efficacy outcome and safety outcome did not differ significantly between the DAPT group and the aspirin-monotherapy group. In the clopidogrel group, the primary end point occurred at a rate of 2.31 per 100 patient-years in the DAPT group and 5.19 per 100 patient-years in the clopidogrel-monotherapy group (hazard ratio, 0.447 [95% CI, 0.258–0.774]). Safety outcome did not differ significantly between groups (0.51 per 100 patient-years versus 0.71 per 100 patient-years, respectively; hazard ratio, 0.730 [95% CI, 0.206–2.588]). Conclusions: The combination of cilostazol and clopidogrel significantly reduced the recurrence of ischemic stroke without increasing the bleeding risk in noncardioembolic, high-risk patients. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01995370. URL: https://www.umin.ac.jp/ctr/; Unique identifier: UMIN000012180.

DOI： 10.1161/STROKEAHA.121.034378

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記述言語：日本語   出版者・発行元：(NPO)日本脳神経血管内治療学会  

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記述言語：日本語   出版者・発行元：(NPO)日本脳神経血管内治療学会  

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記述言語：日本語   出版者・発行元：(NPO)日本脳神経血管内治療学会  

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記述言語：日本語   出版者・発行元：(NPO)日本脳神経血管内治療学会  

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記述言語：日本語   出版者・発行元：(NPO)日本脳神経血管内治療学会  

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記述言語：日本語   出版者・発行元：(NPO)日本脳神経血管内治療学会  

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記述言語：日本語   出版者・発行元：(NPO)日本脳神経血管内治療学会  

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記述言語：日本語   出版者・発行元：(NPO)日本脳神経血管内治療学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

OBJECTIVE: Several studies have investigated the predictors of functional outcome in patients with ischemic stroke after mechanical thrombectomy (MT). However, it is not clear whether pre-stroke cognitive (PSC) impairment is associated with the functional outcome of patients treated with MT. METHODS: We enrolled 113 patients treated with MT from December 2016 to November 2018. PSC was evaluated using the Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE). Poor outcome was defined as a modified Rankin Scale score of 3-6. We compared the clinical characteristics between the groups with poor outcome (n = 61) and good outcome (n = 52) to determine if PSC could be a predictor of poor outcome. RESULTS: IQCODE was significantly higher in the group with poor outcome than good outcome (3.34 vs. 3.13, P = 0.017). Moreover, the following metrics differed between those two groups: age (75.9 vs. 71.6 years old, P = 0.010), the percentage of females (39.9% vs. 17.3%, P = 0.009), the percentage with hypertension (72.1% vs. 44.2%, P = 0.003), National Institutes of Health Stroke Scale (NIHSS) score on admission (20 vs. 11, P < 0.001), and no successful recanalization (24.5% vs. 7.7%; P = 0.025). Multivariable logistic regression analysis demonstrated that PSC (OR: 5.59; 95% CI: 1.55-23.47), history of hypertension (OR: 3.33; 95% CI: 1.29-9.11), no successful recanalization (OR: 5.51; 95% CI: 1.49-25.03), and NIHSS score on admission (OR: 1.14; 95% CI: 1.07-1.22) were associated with poor outcome 3 months after stroke onset. CONCLUSIONS: PSC was significantly and independently associated with poor functional outcome in patients treated with MT.

DOI： 10.1007/s10072-021-05158-6

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記述言語：日本語   掲載種別：研究論文（学術雑誌）  

An 18-year-old man without familial history of neuropathy developed motor and sensory disturbance of bilateral upper limbs after maintaining shoulder abduction/external rotation and elbow flection position of both upper limbs for an hour during military training. Neurological examination and electromyography studies suggested left brachial plexopathy, although a nerve conduction study (NCS) showed mild demyelination of bilateral median nerve and right ulnar nerve. Thoracic outlet syndrome (TOS) was firstly suspected because symptoms were induced by the specific position which narrows, costoclavicular and retropectoralis minor space and cause compression of the brachial plexus; however, no findings suggesting TOS were observed on computed tomography and magnetic resonance imaging. Hence, we suspected a diagnosis of hereditary neuropathy with liability to pressure palsies (HNPP) due to having episodes of bilateral acute brachial plexopathy and mild demyelination on NCS. The diagnosis of HNPP was confirmed by the deletion of the PMP22 gene deletion.

DOI： 10.5692/clinicalneurol.cn-001619

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Background Long-term benefit of dual antiplatelet therapy (DAPT) over single antiplatelet therapy (SAPT) for the prevention of recurrent stroke has not been established in patients with intracranial arterial stenosis. We compared the efficacy and safety of DAPT with cilostazol and clopidogrel or aspirin to those of SAPT with clopidogrel or aspirin in patients with intracranial arterial stenosis, who were recruited to the Cilostazol Stroke Prevention Study for Antiplatelet Combination trial, a randomized controlled trial in high-risk Japanese patients with ischemic stroke. Methods and Results We compared the vascular and hemorrhagic events between DAPT and SAPT in patients with ischemic stroke and symptomatic or asymptomatic intracranial arterial stenosis of at least 50% in a major intracranial artery. Patients were placed in two groups: 275 were assigned to receive DAPT and 272 patients SAPT. The risks of ischemic stroke (hazard ratio [HR], 0.47; 95% CI, 0.23-0.95); and composite of stroke, myocardial infarction, and vascular death (HR, 0.48; 95% CI, 0.26-0.91) were lower in DAPT than SAPT, whereas the risk of severe or life-threatening bleeding (HR, 0.72; 95% CI, 0.12-4.30) did not differ between the 2 treatment groups. Conclusions DAPT using cilostazol was superior to SAPT with clopidogrel or aspirin for the prevention of recurrent stroke and vascular events without increasing bleeding risk among patients with intracranial arterial stenosis after stroke. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT01995370.

DOI： 10.1161/JAHA.121.022575

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記述言語：英語  

DOI： 10.1038/s41598-021-97242-2

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND AND AIM: We determined to investigate the incidence and clinical impact of new cerebral microbleeds after intravenous thrombolysis in patients with acute stroke. METHODS: The THAWS was a multicenter, randomized trial to study the efficacy and safety of intravenous thrombolysis with alteplase in patients with wake-up stroke or unknown onset stroke. Prescheduled T2*-weighted imaging assessed cerebral microbleeds at three time points: baseline, 22-36 h, and 7-14 days. Outcomes included new cerebral microbleeds development, modified Rankin Scale (mRS) ≥3 at 90 days, and change in the National Institutes of Health Stroke Scale (NIHSS) score from 24 h to 7 days. RESULTS: Of all 131 patients randomized in the THAWS trial, 113 patients (mean 74.3 ± 12.6 years, 50 female, 62 allocated to intravenous thrombolysis) were available for analysis. Overall, 46 (41%) had baseline cerebral microbleeds (15 strictly lobar cerebral microbleeds, 14 mixed cerebral microbleeds, and 17 deep cerebral microbleeds). New cerebral microbleeds only emerged in the intravenous thrombolysis group (seven patients, 11%) within a median of 28.3 h, and did not additionally increase within a median of 7.35 days. In adjusted models, number of cerebral microbleeds (relative risk (RR) 1.30, 95% confidence interval (CI): 1.17-1.44), mixed distribution (RR 19.2, 95% CI: 3.94-93.7), and cerebral microbleeds burden ≥5 (RR 44.9, 95% CI: 5.78-349.8) were associated with new cerebral microbleeds. New cerebral microbleeds were associated with an increase in NIHSS score (p = 0.023). Treatment with alteplase in patients with baseline ≥5 cerebral microbleeds resulted in a numerical shift toward worse outcomes on ordinal mRS (median [IQR]; 4 [3-4] vs. 0 [0-3]), compared with those with <5 cerebral microbleeds (common odds ratio 17.1, 95% CI: 0.76-382.8). The association of baseline ≥5 cerebral microbleeds with ordinal mRS score differed according to the treatment group (p interaction = 0.042). CONCLUSION: New cerebral microbleeds developed within 36 h in 11% of the patients after intravenous thrombolysis, and they were significantly associated with mixed-distribution and ≥5 cerebral microbleeds. New cerebral microbleeds development might impede neurological improvement. Furthermore, cerebral microbleeds burden might affect the effect of alteplase.

DOI： 10.1177/17474930211035023

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND AND PURPOSE: In this post-hoc analysis using acute dual study dataset, the impacts of cerebral microbleeds (MBs) after mild stroke on clinical outcome were investigated. METHODS: The number of MBs on admission was categorized as 1) no MBs, 2) MBs 1-4, 3) MBs 5-9, and 4) MBs ≥ 10. The efficacy outcome was defined as neurological deterioration and stroke recurrence within 14 days. Safety outcomes included ICH and/or SAH as well as extracranial hemorrhages. RESULTS: Of the 1102 patients, 780 (71%) had no MBs on admission, while 230 (21%) had MBs 1-4, 48 (4%) had MBs 5-9, and 44 (4%) had MBs ≥ 10. The number of MBs was not associated with the neurological deterioration and/or stroke recurrence (p = 0.934), ICH and/or SAH (p = 0.743), and extracranial hemorrhage (p = 0.205). Favorable outcome was seem in 84% in the No MBs group, 83% in the MBs 1-4, 94% in the MBs 5-9, and 85% in the MBs ≥ 10 (p = 0.304). Combined cilostazol and aspirin therapy did not alter any rates of efficacy and safety outcomes among the no MBs, MBs 1-4, MBs 5-9, and MBs ≥ 10 groups compared to aspirin alone (all p > 0.05). By multivariate regression analysis, a history of ICH and diastolic blood pressure were the independent parameters to all of the MBs criteria (presence, MBs ≥ 5, and MBs ≥ 10). CONCLUSIONS: MBs did not alter the clinical outcome at 3 months of onset. Elevated diastolic blood pressure and a history of ICH were the essential parameters related to the MBs.

DOI： 10.1016/j.jocn.2021.04.028

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記述言語：日本語   出版者・発行元：(一社)日本脳卒中学会  

【背景と目的】動脈硬化性内頸動脈閉塞例では,閉塞部をガイドワイヤーで通過(lesion cross)することが求められる.頸動脈エコーはlesion cross部位を描出できる可能性がある.【方法】2015年4月から2019年5月までの血栓回収療法例中,内頸動脈起始部の動脈硬化性閉塞例を対象とした.再開通療法後に,術前に施行した頸動脈エコー所見を再評価した.【結果】8例のデータを解析でき,6例でlesion cross部位を頸動脈エコーで描出できていた.Lesion cross部位は,周囲の高輝度から等輝度のプラークと区別でき,低輝度を呈する血管腔として捉えられた.Color Doppler法では3例で血流が入り込む像を描出していた.5例のlesion cross部位は,内頸動脈の前面に位置していた.【結論】頸動脈エコーは,動脈硬化性内頸動脈の急性閉塞部の同定に有用な可能性がある.(著者抄録)

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その他リンク： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2021&ichushi_jid=J01786&link_issn=&doc_id=20210802450004&doc_link_id=%2Fdh3strok%2F2021%2F004304%2F004%2F0320-0326%26dl%3D0&url=https%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fdh3strok%2F2021%2F004304%2F004%2F0320-0326%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

記述言語：英語   掲載種別：研究論文（学術雑誌）  

Background and Purpose: We investigated whether the signal change on fluid-attenuated inversion recovery (FLAIR) can serve as a tissue clock that predicts the clinical outcome after endovascular thrombectomy (EVT), independently of the onset-to-admission time. Methods: Consecutive patients with acute stroke treated with EVT between September 2014 and December 2018 were enrolled. Based on the parenchymal signal change on FLAIR, patients were classified into FLAIR-negative and FLAIR-positive groups. The clinical characteristics, imaging findings, EVT parameters, and the intracranial hemorrhage defined as Heidelberg Bleeding Classification ≥1c hemorrhage (parenchymal hemorrhage, intraventricular hemorrhage, subarachnoid hemorrhage, and/or subdural hemorrhage) were compared between the 2 groups. A modified Rankin Scale score 0 to 1 at 3 months was considered to represent a good outcome. Results: Of the 227 patients with EVT during the study period, 140 patients (62%) were classified into the FLAIR-negative group and 87 (38%) were classified into the FLAIR-positive group. In the FLAIR-negative group, the patients were older (P=0.011), the onset-to-image time was shorter (P<0.001), the frequency of cardioembolic stroke was higher (P=0.006), and the rate of intravenous thrombolysis was higher (P<0.001) in comparison to the FLAIR-positive group. Although the rate of complete recanalization after EVT did not differ between the 2 groups (P=0.173), the frequency of both any-intracranial hemorrhage and Heidelberg Bleeding Classification ≥1c hemorrhage were higher in the FLAIR-positive group (P=0.004 and 0.011). At 3 months, the percentage of patients with a good outcome (FLAIR-negative, 41%; FLAIR-positive, 27%) was significantly related to the FLAIR signal change (P=0.047), while the onset-to-image time was not significant (P=0.271). A multivariate regression analysis showed that a FLAIR-negative status was independently associated with a good outcome (odds ratio, 2.10 [95% CI, 1.02–4.31], P=0.044). Conclusions: A FLAIR-negative status may predict the clinical outcome more accurately than the onset-to-admission time, which may support the role of FLAIR as a tissue clock.

DOI： 10.1161/STROKEAHA.120.033374

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記述言語：日本語   掲載種別：研究論文（学術雑誌）  

DOI： 10.5692/clinicalneurol.cn-001587

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記述言語：英語  

DOI： 10.1001/jama.2021.4037

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記述言語：日本語   掲載種別：研究論文（学術雑誌）  

Giant cell arteritis (GCA), also referred to as temporal arteritis, is a variant of large-vessel vasculitis. GCA should be considered in the differential diagnosis in patients aged >50 years, who present with headache, abrupt onset of visual disturbances, unexplained fever, a high erythrocyte sedimentation rate, and high serum C-reactive protein levels. Diagnosis of GCA is based on accurate interpretation of laboratory data, temporal artery biopsy findings, and imaging study results. Imaging modalities used for GCA include positron emission tomography, computed tomography (CT), CT angiography, and conventional magnetic resonance angiography. Biopsy is the gold standard for diagnosis of GCA. Glucocorticoids (GCs) are used as standard treatment to induce remission and also for maintenance therapy. However, clinicians should be aware of the adverse effects of GC treatment, including hyperglycemia, an immunocompromised state, and delirium. If adverse effects outweigh the benefits of GC treatment, it is necessary to consider switching to or adding an immunosuppressant to the therapeutic regimen.

DOI： 10.11477/mf.1416201791

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Our previous trial acute dual study (ADS) reported that dual antiplatelet therapy (DAPT) using cilostazol and aspirin did not reduce the rate of short-term neurological worsening in non-cardioembolic stroke patients. Present post-hoc analysis investigated whether the impact of combined cilostazol and aspirin differed among stroke subtypes and factors associated with neurological deterioration and/or stroke recurrence. METHODS: Using the ADS registry, the rate of neurological deterioration, defined as clinical worsening and/or recurrent stroke, including transient ischemic attack was calculated. Stroke subtypes included large-artery atherosclerosis (LAA), small vessel occlusion (SVO), other determined etiology (Others), and undetermined etiology of stroke (Undetermined). RESULTS: Data of 1022 patients were analyzed. Deterioration was seen in 104 (10%) patients, and the rates were not markedly different between patients treated with DAPT vs. aspirin in any stroke subtypes: LAA, 19% vs. 11%, (p=0.192); SVO, 10% vs. 10% (p=1.000); Others, 6% vs. 6% (p=1.000); Undetermined, 11% vs. 8% (p=0.590). Diabetes mellitus was the independent factor associated with deterioration (odds ratio 4.360, 95% confidence interval 1.139-16.691, p=0.032) in the LAA group. Age (1.030 [1.004-1.057], p=0.026), systolic blood pressure (1.012 [1.003-1.022], p=0.010), and infarct size (2.550 [1.488-4.371], p=0.001) were associated with deterioration in SVO group, and intracranial stenosis/occlusion was associated with it in the Undetermined group (3.744 [1.138-12.318], p=0.030). CONCLUSIONS: Combined cilostazol and aspirin did not reduce the rate of short-term neurological deterioration in any clinical stroke subtype. The characteristics of patients whose condition deteriorates in the acute period may differ based on the stroke subtypes.

DOI： 10.1016/j.jstrokecerebrovasdis.2020.105494

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記述言語：日本語   掲載種別：研究論文（学術雑誌）  

A 79-year-old woman developed consciousness disturbance, left eye deviation, right hemiplegia and aphasia with hypoxemia. Chest X-ray showed bilateral pulmonary edema. MRI revealed the left internal carotid artery occlusion and entire left middle cerebral artery infarct including insular cortex. We performed mechanical thrombectomy therapy and TICI3 recanalization was obtained. During operation, the respiratory condition deteriorated and the ventilator was started after mechanical thrombectomy therapy. Chest X-ray showed butterfly shadow, which indicated pulmonary edema. Pulmonary edema improved on the 2nd day of onset, and disappeared on the 3rd day. There was no heart diseases such as Takotsubo myocardiopathy, acute cardiac failure and cardiomyopathy on echocardiography and electrocardiography. Therefore, we diagnosed her as having neurogenic pulmonary edema due to cerebral infarction including insular cortex. We consider that left insular cortex infarction was a trigger of neurogenic pulmonary edema. If hypoxemia associated with infarction including the insular cortex, neurogenic pulmonary edema should be considered for medical treatment.

DOI： 10.5692/clinicalneurol.cn-001491

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

IMPORTANCE: Whether intravenous thrombolysis is needed in combination with mechanical thrombectomy in patients with acute large vessel occlusion stroke is unclear. OBJECTIVE: To examine whether mechanical thrombectomy alone is noninferior to combined intravenous thrombolysis plus mechanical thrombectomy for favorable poststroke outcome. DESIGN, SETTING, AND PARTICIPANTS: Investigator-initiated, multicenter, randomized, open-label, noninferiority clinical trial in 204 patients with acute ischemic stroke due to large vessel occlusion enrolled at 23 hospital networks in Japan from January 1, 2017, to July 31, 2019, with final follow-up on October 31, 2019. INTERVENTIONS: Patients were randomly assigned to mechanical thrombectomy alone (n = 101) or combined intravenous thrombolysis (alteplase at a 0.6-mg/kg dose) plus mechanical thrombectomy (n = 103). MAIN OUTCOMES AND MEASURES: The primary efficacy end point was a favorable outcome defined as a modified Rankin Scale score (range, 0 [no symptoms] to 6 [death]) of 0 to 2 at 90 days, with a noninferiority margin odds ratio of 0.74, assessed using a 1-sided significance threshold of .025 (97.5% CI). There were 7 prespecified secondary efficacy end points, including mortality by day 90. There were 4 prespecified safety end points, including any intracerebral hemorrhage and symptomatic intracerebral hemorrhage within 36 hours. RESULTS: Among 204 patients (median age, 74 years; 62.7% men; median National Institutes of Health Stroke Scale score, 18), all patients completed the trial. Favorable outcome occurred in 60 patients (59.4%) in the mechanical thrombectomy alone group and 59 patients (57.3%) in the combined intravenous thrombolysis plus mechanical thrombectomy group, with no significant between-group difference (difference, 2.1% [1-sided 97.5% CI, -11.4% to ∞]; odds ratio, 1.09 [1-sided 97.5% CI, 0.63 to ∞]; P = .18 for noninferiority). Among the 7 secondary efficacy end points and 4 safety end points, 10 were not significantly different, including mortality at 90 days (8 [7.9%] vs 9 [8.7%]; difference, -0.8% [95% CI, -9.5% to 7.8%]; odds ratio, 0.90 [95% CI, 0.33 to 2.43]; P > .99). Any intracerebral hemorrhage was observed less frequently in the mechanical thrombectomy alone group than in the combined group (34 [33.7%] vs 52 [50.5%]; difference, -16.8% [95% CI, -32.1% to -1.6%]; odds ratio, 0.50 [95% CI, 0.28 to 0.88]; P = .02). Symptomatic intracerebral hemorrhage was not significantly different between groups (6 [5.9%] vs 8 [7.7%]; difference, -1.8% [95% CI, -9.7% to 6.1%]; odds ratio, 0.75 [95% CI, 0.25 to 2.24]; P = .78). CONCLUSIONS AND RELEVANCE: Among patients with acute large vessel occlusion stroke, mechanical thrombectomy alone, compared with combined intravenous thrombolysis plus mechanical thrombectomy, failed to demonstrate noninferiority regarding favorable functional outcome. However, the wide confidence intervals around the effect estimate also did not allow a conclusion of inferiority. TRIAL REGISTRATION: umin.ac.jp/ctr Identifier: UMIN000021488.

DOI： 10.1001/jama.2020.23522

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND AND PURPOSE: We determined to identify patients with unknown onset stroke who could have favorable 90-day outcomes after low-dose thrombolysis from the THAWS (Thrombolysis for Acute Wake-Up and Unclear-Onset Strokes With Alteplase at 0.6 mg/kg) database. METHODS: This was a subanalysis of an investigator-initiated, multicenter, randomized, open-label, blinded-end point trial. Patients with stroke with a time last-known-well >4.5 hours who showed a mismatch between diffusion-weighted imaging (DWI) and fluid-attenuated inversion recovery were randomly assigned (1:1) to receive alteplase at 0.6 mg/kg intravenously or standard medical treatment. The patients were dichotomized by ischemic core size or National Institutes of Health Stroke Scale score, and the effects of assigned treatments were compared in each group. The efficacy outcome was favorable outcome at 90 days, defined as a modified Rankin Scale score of 0 to 1. RESULTS: The median DWI-Alberta Stroke Program Early CT Score (ASPECTS) was 9, and the median ischemic core volume was 2.5 mL. Both favorable outcome (47.1% versus 48.3%) and any intracranial hemorrhage (26% versus 14%) at 22 to 36 hours were comparable between the 68 thrombolyzed patients and the 58 control patients. There was a significant treatment-by-cohort interaction for favorable outcome between dichotomized patients by ASPECTS on DWI (P=0.026) and core volume (P=0.035). Favorable outcome was more common in the alteplase group than in the control group in patients with DWI-ASPECTS 5 to 8 (RR, 4.75 [95% CI, 1.33-30.2]), although not in patients with DWI-ASPECTS 9 to 10. Favorable outcome tended to be more common in the alteplase group than in the control group in patients with core volume >6.4 mL (RR, 6.15 [95% CI, 0.87-43.64]), although not in patients with volume ≤6.4 mL. The frequency of any intracranial hemorrhage did not differ significantly between the 2 treatment groups in any dichotomized patients. CONCLUSIONS: Patients developing unknown onset stroke with DWI-ASPECTS 5 to 8 showed favorable outcomes more commonly after low-dose thrombolysis than after standard treatment. Registration: URL: https://www.clinicaltrials.gov; Unique Identifier: NCT02002325. URL: https://www.umin.ac.jp/ctr; Unique Identifier: UMIN000011630.

DOI： 10.1161/STROKEAHA.120.030848

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記述言語：日本語   出版者・発行元：(公社)日本皮膚科学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Objective Computed tomography (CT) can be used for visualizing acute intracerebral hemorrhages (ICHs) as distinct hyperdense areas and cerebral edema as perihematomal low-density areas (LDAs). We observed a perihematomal LDA on CT, which appeared to be part of a hemorrhage on magnetic resonance imaging (MRI) in acute ICH. We named this "CT perihematomal rim" and evaluated its characteristics and clinical significance. Methods We stratified patients with acute ICH according to the presence or absence of a CT perihematomal rim and then compared their radiologic findings. Logistic regression analyses were performed to assess whether the CT findings can predict the presence of a CT perihematomal rim. Patients Patients within 24 hours of ICH onset who were admitted between September 1, 2014, and October 31, 2018, were registered. Results Overall, 139 patients (91 men; mean age, 66 years) were investigated. CT perihematomal rims were observed in 40 patients (29%). ICH volumes on CT were 30% smaller than those on MRI in patients with CT perihematomal rims. On a multivariate analysis, the presence of a CT perihematomal rim was independently associated with the maximum diameter of the perihematomal LDA. According to a receiver operating characteristic analysis, the maximum LDA diameter threshold was 7.5 mm (sensitivity, 85%; specificity, 83%). Conclusion CT perihematomal rims were observed in 29% of the patients with acute ICH. A perihematomal LDA (>7.5 mm) in acute ICH cases should be considered a CT perihematomal rim. Clinicians should be aware that the ICH volume on CT may be underestimated by 30%.

DOI： 10.2169/internalmedicine.6653-20

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

INTRODUCTION: Intracerebral hemorrhage (ICH) is a devastating hemorrhagic event and is associated with high mortality or severe neurological sequelae. Age-associated differences in hematoma location for nonlobar ICH are not well known. The aims of the present study were to elucidate the relationship between age and hematoma location and to assess the differences in small-vessel disease (SVD) burden as a potential surrogate marker for longstanding hypertension among various hematoma locations. METHODS: From September 2014 through July 2019, consecutive patients with acute, spontaneous ICH were retrospectively enrolled from a prospective registry. Magnetic resonance imaging was performed during admission, and the total SVD burden score (including microbleeds, lacunes, enlarged perivascular spaces, and white matter hyperintensities) was calculated. The relationships of hematoma location with aging and SVD burden were assessed by using multivariate logistic regression analyses. RESULTS: A total of 444 patients (156 women [35%]; median age 69 [interquartile range 59-79] years; National Institutes of Health Stroke Scale score 9 [17][3-17]) were enrolled in the present study. Multivariate logistic regression analyses showed that advanced age was independently associated with thalamic (odds ratio [OR]: 1.48, 95% confidence interval [CI]: 1.19-1.84, p < 0.001 for 10-year increment) and lobar hemorrhage (OR: 1.58, 95% CI: 1.19-2.09, p = 0.002) and was independently and negatively related to putaminal hemorrhage (OR: 0.55, 95% CI: 0.44-0.68, p < 0.001). The total SVD burden score was independently and positively associated with thalamic hemorrhage (OR: 1.27, 95% CI: 1.01-1.59, p = 0.045) and negatively with lobar hemorrhage (OR: 0.74, 95% CI: 0.55-0.99, p = 0.042), even after adjusting by age, but not with putaminal hemorrhage (OR: 0.91, 95% CI: 0.73-1.14, p = 0.395). CONCLUSION: Putaminal, thalamic, and lobar hemorrhages are prone to occur in specific ages and SVD states: putaminal in young patients, thalamic in old and high SVD burden patients, and lobar hemorrhages in old and low SVD burden patients. Susceptibility to bleeding with aging or severe SVD accumulation seems to differ considerably among brain locations.

DOI： 10.1159/000515411

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記述言語：日本語   掲載種別：研究論文（学術雑誌）  

The Japanese Society of Neurology has held an annual workshop for stroke education since September 2018 for young members of the society and medical students to take an interest in stroke medicine and stroke research and to contribute to conquest of stroke, a national disease. The third annual workshop will be held in the National Cerebral and Cardiovascular Center, Osaka in September 2020 also with the support of the Japan Stroke Society. Designated lecturers are preparing for presentation of their own devising. Here, brief abstracts of educational lectures and special statements on career formation of vascular neurologists are introduced.

DOI： 10.5692/clinicalneurol.cn-001515

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: The feasibility of performing MRI first for patients with suspected hyperacute stroke in real-world practice has not been fully examined. Moreover, most past studies of reducing door-to-reperfusion time (DRT) in endovascular treatment (EVT) were conducted using CT. The aim of this study was to evaluate the feasibility of an MRI-first policy and to examine the effects of a quality improvement (QI) process for reducing DRT using MRI. METHODS: From January 2013 to December 2018, consecutive patients with acute stroke who came to hospital directly and were treated with emergent EVT were prospectively enrolled into the present study. In principle, MRI was performed first for patients with suspected acute stroke. A step-by-step QI process for decreasing DRT was adopted during this period. Time metrics for EVT were compared between specific time periods. RESULTS: A total of 180 patients (71 women; median age 76 years (range 69-64); National Institutes of Health Stroke Scale score 17 (range 10-23)) were included in the present study. More patients in the late phase were managed with the MRI-first policy (p<0.001). DRT (199 min in Phase 1, 135 min in Phase 2, 129 min in Phase 3, and 121 min in Phase 4, p<0.001) was significantly reduced across the phases. The percentage of patients with DRT <120 min increased significantly across time periods (p<0.001). Symptomatic intracerebral hemorrhage did not increase across phases (p=0.575). CONCLUSION: An MRI-first policy was feasible, and DRT decreased considerably with a step-by-step QI process. This process may be applicable to other hospitals.

DOI： 10.1136/neurintsurg-2019-015625

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

PURPOSE: This study aimed to evaluate the risk factors, etiology, and outcomes of ischemic stroke (IS) in Japanese young adults. METHODS: This was a prospective multicenter study. We enrolled patients aged 16 to 55 years with IS within seven days of the onset of symptoms. We assessed the demographic data, risk factors, stroke etiology, and outcome at discharge. The clinical characteristics were compared between sexes and among age groups. RESULTS: We prospectively enrolled 519 patients (median age, 48 years: 139 females). The mean National Institute of Health Stroke Scale score was 3.6 ± 0.2. The most common risk factors were hypertension (HT) (55%), dyslipidemia (DL) (47%), and current smoking (42%). Body mass index, incidence of current smoking, and heavy alcohol consumption were higher in males. The prevalence of current smoking, HT, DL, and diabetes mellitus increased with aging. The most common etiologic subgroup of IS was small vessel disease (145/510, 28%). Intracranial arterial dissection (IAD) was the most common among the other determined causes (56/115, 49%). The outcome at discharge was relatively good (mRS 0-1, 71.7%); however, poor outcome (mRS ≥ 4) was observed at an incidence of 9.5%. CONCLUSIONS: Most young adults with IS had modifiable risk factors, of which prevalence increased with age. This emphasizes lifestyle improvement to prevent IS in the young population. Furthermore, we indicated that the incidence rate of IAD was high among the other determined causes.

DOI： 10.1016/j.jns.2020.117068

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記述言語：英語  

Aortogenic embolic stroke (AES) is an important stroke mechanism. However, as many stroke patients have aortic atheromatous lesions, it is unclear whether these lesions are the cause of these strokes. Cholesterol crystals are the solid, crystalline form of cholesterol that is found in atherosclerosis, but not in cardiac diseases such as atrial fibrillation, valvular diseases, and cardiomyopathy. Therefore, if a cholesterol crystal is found in a thrombus removed by mechanical thrombectomy (MT), this makes it possible to diagnose a patient as having an atheromatous lesion. Here, we report an AES case with a cholesterol crystal found in a thrombus removed by MT. A 67-year-old man was admitted due to consciousness disturbance, aphasia, and right hemiplegia. Diffusion-weighted imaging (DWI) showed a hyperintense area in the left frontal lobe, and magnetic resonance angiography demonstrated a branch occlusion of the left middle cerebral artery (MCA). MT was performed 1.5 h after stroke onset, with the thrombus removed and a left occluded MCA completely recanalized. Carotid duplex ultrasonography did not reveal any plaque in the carotid artery. Echocardiography did not show any abnormal function or findings, including thrombus. Transesophageal echocardiography showed a 4.9 mm atheromatous lesion at the aortic arch. Therefore, we suspected this patient as having an AES due to the embolic source of atheromatous lesion at the aortic arch. Pathological examination of the embolus revealed a cholesterol crystal cleft in the thrombus. Therefore, we diagnosed this patient as having AES caused by an atheromatous lesion at the aortic arch.

DOI： 10.1016/j.jstrokecerebrovasdis.2020.105178

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: The long-term outcome in acute stroke patients with large vessel occlusion (LVO) treated with endovascular therapy (EVT) are unclear. We investigated functional outcomes one year after EVT in acute stroke patients with LVO. METHODS: We retrospectively enrolled 149 stroke patients with LVO who underwent EVT from our prospective stroke registry. We assessed modified Rankin Scale (mRS) scores at one year from onset. The degree of recanalization was evaluated using modified thrombolysis in cerebral infarction (mTICI) grades. Good recanalization and a favorable outcome were defined as an mTICI grade ≥ 2b and mRS score ≤ 2, respectively. RESULTS: Favorable outcomes were observed in 76 (51.0%) patients. The favorable outcome group was younger (median age: 72 [interquartile range, 63-79] years vs. 79 [70-84] years, P < .001) and had more male patients (79% vs. 60%, P = .013), lower National Institutes of Health Stroke Scale scores at admission (median 14 [7-18]) vs. 19 [15-25], P < .001), higher DWI-ASPECTS upon admission (median [6-9] vs. 6 [4-8], P = .022), more patients with mTICI ≥ 2b (93% vs. 64%, P < .001) and fewer post-therapy intracranial cerebral hemorrhages (13% vs. 29%, P = .019) than the poor outcome group. In our multivariate analysis, mTICI ≥ 2b were independently associated with favorable outcomes at one year from onset (odds ratio, 10.282; 95% confidence interval, 1.587-66.604; P = .015). CONCLUSIONS: Good recanalization was associated with favorable functional outcomes one year after EVT in acute stroke patients with LVO.

DOI： 10.1016/j.jns.2020.117009

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Stroke is the most prevalent cardiovascular disease worldwide, and is still one of the leading causes of death and disability. Stem cell-based therapy is actively being investigated as a new potential treatment for certain neurological disorders, including stroke. Various types of cells, including bone marrow mononuclear cells, bone marrow mesenchymal stem cells, dental pulp stem cells, neural stem cells, inducible pluripotent stem cells, and genetically modified stem cells have been found to improve neurological outcomes in animal models of stroke, and there are some ongoing clinical trials assessing their efficacy in humans. In this review, we aim to summarize the recent advances in cell-based therapies to treat stroke.

DOI： 10.3390/ijms21186718

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND AND PURPOSE: We investigated the impact of complete recanalization beyond partial recanalization in distal (M2) middle cerebral artery (MCA) occlusion. METHODS: Data regarding M2 occlusion patients treated with endovascular thrombectomy (EVT) and/or intravenous thrombolysis (tPA) were reviewed from our prospective EVT registry and multicenter tPA (YAMATO study) data bank. Complete recanalization was modified thrombolysis with cerebral infarction score (TICI) of 3 at the end of EVT or similar appearances of both MCAs on magnetic resonance angiography (MRA) within 1.5 h after tPA. Partial recanalization was defined as TICI ≥2b or > 50% recanalization on MRA. At 3 months, favorable outcome was defined as a modified Rankin Scale score ≤ 2. RESULT: Data on 121 patients were analyzed. EVT-alone was in 38 patients; combined EVT and tPA in 28; and tPA-alone in 55. Complete recanalization was achieved in 27 (22%), partial recanalization in 48 (40%), and no-to-limited recanalization in 46 (38%). At 3 months, 51% of patients had favorable outcomes, and this rate was significantly higher in the complete recanalization group than in the partial and no-to-limited recanalization groups (75% vs. 41% vs. 49%, p = .043). Multivariate regression analysis showed that complete recanalization was an independent parameter related to favorable outcomes (odds ratio 4.78, 95% CI: 1.16-19.73, p = .030). However, combined complete and partial recanalization was not associated with favorable outcomes (odds ratio 1.49, 95% CI 0.53-4.22, p = .449). CONCLUSION: Complete recanalization, but not partial recanalization, at the end of EVT and tPA therapy is associated with favorable outcomes in patients with M2 occlusion.

DOI： 10.1016/j.jns.2020.116873

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掲載種別：研究論文（学術雑誌）  

© 2020 Elsevier B.V. Background: The cardio-ankle vascular index (CAVI) has been proposed as a useful parameter for arteriosclerotic diseases. However, whether it is associated with stroke risk in Japanese subjects remains unclear. Methods: In total, 280 Japanese subjects (92 females, 52.6 ± 5 years old) underwent a medical check-up. CAVI value and risk factors for arterial dysfunction were evaluated; the predicted 10-year stroke risk was measured by the Japan Public Health Center study. Results: Age, sex, body mass index, and systolic blood pressure were significant independent predictors of CAVI. CAVI values were significantly elevated in the high, compared with the medium-low and low predicted risk groups. A significant odds ratio (OR) for the high-risk group was noted in the highest quartile of CAVI values (OR, 14.67; 95% confidence interval [CI], 3.17–68.0), compared with the lowest quartile, after adjusting for potential confounders. A significant OR for very high predicted stroke risk was also found for each quartile increase (OR, 3.04; 95% CI, 1.87–4.94) and 1-standard deviation increase (OR, 2.24; 95% CI, 1.52–3.30) in CAVI value. Conclusion: Elevated CAVI values were related to an elevated predicted stroke risk, suggesting that CAVI could be a suitable surrogate marker for finding subjects at an increased risk of first-ever stroke.

DOI： 10.1016/j.jns.2020.116862

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Urinary liver-type fatty-acid binding protein (L-FABP), which is a biomarker of kidney tubule injury, has been studied extensively and established as a risk marker of acute kidney injury (AKI). However, no evidence has indicated whether kidney tubule injury is associated with the development of AKI and mortality in patients with acute ischemic stroke. METHODS: Acute ischemic stroke patients hospitalized in the stroke care unit (SCU) within 24 hours after symptom onset were prospectively investigated. AKI was defined on the basis of Kidney Disease: Improving Global Outcomes (KDIGO) criteria. Baseline urinary L-FABP was measured upon admission. We evaluated the association among urinary L-FABP, the incidence of AKI, and 90-day mortality adjusted for renal function, albuminuria, and other potentially predictive variables using the multivariable analysis. RESULTS: In total, 527 acute ischemic stroke patients (342 males; median age 74 years) were enrolled to the study. Twenty-seven patients (5.1%) occurred AKI within 7 days after admission. In the univariate analysis, high urinary L-FABP level had positive associations with AKI (53.8 μg/g Cr vs. 3.9 μg/g Cr, P<0.001) and 90-day mortality (15.5 μg/g Cr vs. 4.0 μg/g Cr, P<0.001). In the multivariate analysis, elevated urinary L-FABP level (per 10 μg/g Cr increase) was independently associated with AKI (Odds ratio 1.225; 95% confidence interval (CI), 1.083-1.454, P=0.003) and 90-day mortality (Hazard ratio 1.091; 95% CI, 1.045-1.138, P<0.001). CONCLUSION: Urinary biomarker of kidney tubule injury is independently associated with the development of AKI and 90-day mortality in patients with acute ischemic stroke treated at the SCU.

DOI： 10.1111/ene.14448

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：WILEY  

A 30-year-old woman presented with paresthesia in her left lower limb and blurred vision. She had bilateral horizontal gaze palsy with the absence of cranial nerve symptoms such as horizontal saccades, pursuit, and facial nerve palsy. Considering her convalescence, we speculated that her pure bilateral horizontal gaze palsy was mainly caused by disturbance in paramedian pontine reticular formation (PPRF). Pure horizontal gaze palsy may also be a characteristic feature of multiple sclerosis.

DOI： 10.1111/ncn3.12395

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

OBJECTIVE: Some hyperacute stroke patients have unfavorable outcomes after endovascular thrombectomy (EVT) despite successful recanalization. We hypothesized that a cardiac parameter, moderate-to-severe mitral regurgitation (MR), might decrease the rate of favorable clinical outcome after EVT in patients with atrial fibrillation (AF). METHOD: From our prospective EVT registry, AF patients who underwent transthoracic echocardiography (TTE) were retrospectively analyzed. Based on the presence of moderate-to-severe MR, patients were assigned to either significant MR or nonsignificant MR group. The severity of MR was determined by the ratio of the color Doppler jet area to the left atrial area in mid-systole. Moderate-to-severe MR was estimated to be at a ratio of >20%. Favorable outcome was defined as having a modified Rankin Scale score of 0-1 at 3 months. RESULT: 127 patients with AF who underwent TTE were included in the study. TTE results found that 25 (20%) patients had significant MR. Patients with significant MR were older (p = 0.051) and had enlarged left (p = 0.015) and right (p = 0.002) atria. Tricuspid and aortic regurgitation (p = 0.007 and 0.043, respectively) were more severe in significant MR group. At 3 months, favorable outcomes were 11% in the significant MR group and 26% in the non-significant MR group (p = 0.031). Multivariate regression analysis reported that moderate-to-severe MR was a negative predictor of favorable outcome (odds ratio = 0.14; 95% confidence interval = 0.02, 0.84; p = 0.031). CONCLUSIONS: Significant MR might prevent the clinical recovery of AF patients.

DOI： 10.1080/01616412.2020.1773611

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Myeloproliferative neoplasms (MPNs) including polycythemia vera (PV) and essential thrombocythemia (ET) have an increased risk of ischemic stroke. However, little is known about brain morphological changes and the cerebral vasculature in MPNs. The aim of the present study is to clarify the prevalence rates of brain infarcts (BIs) on magnetic resonance imaging (MRI) and to assess the detailed clinical and MRI characteristics in those patients. METHODS: We prospectively enrolled patients with MPNs who underwent brain MRI between September 2017 and June 2019. BI patterns were characterized by the numbers and locations of BIs on MRI. RESULTS: A total of 101 patients were included in the present study. BIs were observed in 23 patients (23%). Multiple logistic regression analysis showed that age > 60 years (odds ratio (OR) 7.34, 95% confidence interval (CI) 1.08-49.7, p = .041) and history of thrombosis (OR 40.6, 95% CI 7.97-207, p < .0001) were independently associated with BIs, but not the JAK2V617F mutation. Of the 23 patients with BIs, eight patients (35%) had multiple territorial infarcts, and large vessel involvement was identified in five patients (22%). Two patients had thrombus formation in large vessels. CONCLUSIONS: Among patients with MPNs who underwent MRI, BIs were observed in 23% of patients followed up in our center. Older age and thrombosis history were independently associated with BIs. Some patients with MPNs may present with distinctive MRI findings including multiple territorial infarcts and thrombus formation in large vessels.

DOI： 10.1016/j.jns.2020.116990

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: We hypothesized that administration of cilostazol may clarify the occult atrial fibrillation (AF) during hospitalization in mild stroke patients, who has no history of AF. METHODS: From our prospective non-cardioembolic stroke study, randomized to dual antiplatelet therapy using cilostazol and aspirin or aspirin alone trial (ADS), data on the presence or absence of AF were retrospectively analyzed. In the ADS, during hospitalization, as a routine examination, presence of AF was investigated using electrocardiogram (ECG), ECG monitoring and Holter ECG. Multivariate regression analysis was conducted to evaluate the independent parameters related to the AF. Clinical outcome at 3 months was evaluated using modified Rankin Scale (mRS) score. RESULTS: Data on 1194 patients (793 [66%] men; median age [interquartile range] of 69 [61-77] years, National Institutes of Health Stroke Scale score 2 [1-4], onset-to-admission 10.8 [4.7-20.5] hours) were retrospectively analyzed. AF was newly detected in 41 (3%) patients (3 by ECG, 21 by the ECG monitoring and 17 by the Holter ECG) during hospitalization. Patients treated with combined cilostazol and aspirin therapy frequently had the AF than those took aspirin alone (5% vs. 2%, p = .007). Multivariate regression analysis showed that cilostazol administration was one of the independent factors for new-AF (odds ratio 2.672, 95%CI: 1.205-5.927, p = .016). The frequency of mRS 0-1 was 68% in the new-AF group and 67% in the non-AF group (p = 1.000). CONCLUSION: Cilostazol therapy may increase the detectability of AF in acute non-cardioembolic stroke, though the new-AF was not related to clinical outcome at 3 months.

DOI： 10.1016/j.jns.2020.116796

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記述言語：日本語   掲載種別：研究論文（学術雑誌）  

A 88-year-old man suddenly presented with aphasia and right hemiparesis. The diffusion-weighted image of MRI showed ischemic lesions on the left middle cerebral artery area, and MRA showed the left intracranial artery (ICA) occlusion. Therefore, we diagnosed him as having acute ischemic stroke and treated with mechanical thrombectomy (MT). The DWI of MRI showed ischemic lesions on the left middle cerebral artery area, and MRA showed the left ICA occlusion. Therefore, we performed MT and continued best medical treatment, but ICA was reoccluded. Six day later, aspergillus was found in the thrombus from ICA. Then, we considered that ICA occlusion was caused by aspergillus. We experienced a patient specified the cause by thrombus pathology. The pathological diagnosis of the thrombus getting by MT is usefulness for stroke etiology.

DOI： 10.5692/clinicalneurol.cn-001400

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

OBJECTIVE: We examined the diagnostic value of brain perfusion single-photon emission computed tomography (SPECT) using voxel-based statistical analysis with CT-based attenuation correction (CT-AC) by comparing it to that with Chang's AC in mild cognitive impairment (MCI) patients and attempted to locate brain areas that are good indicators predicting the progression of MCI. METHODS: Twenty-six individuals matched for age, educational background and initial Mini-Mental State Examination (MMSE) score of more than 24 underwent SPECT with N-isopropyl-4-[123I]iodoamphetamine and were assigned to 2 groups: the stable MCI (S-MCI) group comprising 11 subjects who maintained their MMSE score (mean 27.0) during at least a 1-year follow-up period (mean 37.2 months) and the progressive MCI (P-MCI) group comprising 15 subjects whose MMSE scores decreased by 3 or more points (from 26.4 to 21.4, mean). The diagnostic values of the two AC methods for discriminating P-MCI from S-MCI were compared using voxel-based statistical analysis in the lobe (Level 2) and lobule/gyrus levels (Level 3). RESULTS: Receiver operating characteristic analysis revealed that the area under the curve (AUC) was higher with CT-AC than with Chang's AC in the left temporal and limbic lobes in Level 2. In Level 3, the AUC in the left middle temporal gyrus was higher with CT-AC (0.852) than with Chang's AC (0.827). There were differences between the gyri/lobules that showed higher AUCs with CT-AC and those that showed higher AUCs with Chang's AC. When the gyri with the 4 highest AUCs were combined, AUC (0.897) and accuracy (84.6%) were better with CT-AC than with Chang's AC (0.806 and 80.8%). Surprisingly, the AUCs in the posterior cingulate gyrus and precuneus, excluding the AUC in the right precuneus with Chang's AC (0.715), were no more than 0.70 and less useful. CONCLUSIONS: CT-AC may allow brain perfusion SPECT to reflect more exact neuropathic changes in MCI that would cause progression of early AD. CT-AC in conjunction with voxel-based statistical analysis could possess higher diagnostic accuracy for exacerbation of disease implying early Alzheimer changes in MCI patients, with decreases in cerebral perfusion in the left temporal and limbic lobes representing good indicators.

DOI： 10.1007/s12149-020-01477-4

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Guillain-Barré syndrome (GBS) comprises a group of polyneuropathies characterized by rapid progression of limb paralysis. Various subtypes of GBS have been reported. The oculopharyngeal subtype of GBS is currently understood to be primarily a cranial polyneuropathy without limb weakness or cerebellar ataxia. In our case of 62-year-old man, gastrointestinal infection was followed by paranesthesia of the hands. He had bilateral ptosis, pharyngeal disorder, and tongue and bifacial weakness. We diagnosed oculopharyngeal subtype of GBS. It responded to intravenous immunoglobulin. This case highlights the need for further characterization of unusual GBS subtypes.

DOI： 10.2169/internalmedicine.3395-19

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記述言語：日本語   出版者・発行元：(一社)日本神経学会  

症例は88歳の男性である。右麻痺、失語を認め救急搬送された。来院時の頭部MRI/Aにて左中大脳動脈領域に新規梗塞巣と左内頸動脈の閉塞を認めたため、機械的脳血栓回収療法を施行した。その後内科的治療を行うも、左内頸動脈は再閉塞した。血栓病理でアスペルギルス真菌塊を認めた。副鼻腔炎と骨破壊を認めており、アスペルギルスが内頸動脈に直接浸潤し、血栓を形成し、閉塞したことが考えられた。血栓病理によって原因の特定に至った症例を経験した。原因不明の脳梗塞は、機械的血栓回収療法によって回収された血栓を確認することで、原因が判明する可能性がある。(著者抄録)

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その他リンク： https://search-tp.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2020&ichushi_jid=J01550&link_issn=&doc_id=20200602480005&doc_link_id=1390285300159919360&url=https%3A%2F%2Fcir.nii.ac.jp%2Fcrid%2F1390285300159919360&type=CiNii&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00003_3.gif

記述言語：英語   掲載種別：研究論文（学術雑誌）  

OBJECTIVES: Evaluation of cognitive status is not performed routinely in the acute stroke setting. This study aimed to evaluate the frequency of early cognitive impairment in patients with minor ischemic stroke, analyze the factors associated with early cognitive impairment, and assess functional outcomes. METHODS: In this prospective study, 112 consecutive patients with acute minor ischemic stroke were enrolled. Neuroimages were assessed for semiquantitative evaluation of brain atrophy and small vessel disease (SVD) markers. Cognitive performance was measured within 5 days of onset using Montreal Cognitive Assessment (MoCA) scores. Functional outcome analyses were adjusted for demographic variables, premorbid cognitive status, education level, vascular risk factors, neuroimaging characteristics, stroke severity, and MoCA scores. RESULTS: The median MoCA score was 22, and 63% of patients had cognitive impairment. Factors independently associated with cognitive impairment were education (odds ratios [OR], .79; confidence intervals [CI], .63-.99), smoking (OR, .26; 95%CI, .073-.89), and temporal horn atrophy (OR, 4.73; 95% CI, 1.66-13.49). Factors independently associated with poor functional outcome were total MoCA score (OR, .78; 95%CI, .62-.95) and the sum of 4 MoCA subscores (visuospatial/executive, attention, language, and orientation; OR, .72; 95%CI, .53-.92). The cutoff value of the sum of 4 MoCA subscores for predicting poor outcome was 13 points with 76.5% sensitivity and 81.1% specificity. CONCLUSIONS: Early cognitive impairment was common after minor ischemic stroke and was associated with preexisting temporal horn atrophy but not SVD markers. The sum of 4 MoCA subscores was useful in predicting the functional outcome.

DOI： 10.1016/j.jstrokecerebrovasdis.2020.104749

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Background and Purpose- We assessed whether lower-dose alteplase at 0.6 mg/kg is efficacious and safe for acute fluid-attenuated inversion recovery-negative stroke with unknown time of onset. Methods- This was an investigator-initiated, multicenter, randomized, open-label, blinded-end point trial. Patients met the standard indication criteria for intravenous thrombolysis other than a time last-known-well >4.5 hours (eg, wake-up stroke). Patients were randomly assigned (1:1) to receive alteplase at 0.6 mg/kg or standard medical treatment if magnetic resonance imaging showed acute ischemic lesion on diffusion-weighted imaging and no marked corresponding hyperintensity on fluid-attenuated inversion recovery. The primary outcome was a favorable outcome (90-day modified Rankin Scale score of 0-1). Results- Following the early stop and positive results of the WAKE-UP trial (Efficacy and Safety of MRI-Based Thrombolysis in Wake-Up Stroke), this trial was prematurely terminated with 131 of the anticipated 300 patients (55 women; mean age, 74.4±12.2 years). Favorable outcome was comparable between the alteplase group (32/68, 47.1%) and the control group (28/58, 48.3%; relative risk [RR], 0.97 [95% CI, 0.68-1.41]; P=0.892). Symptomatic intracranial hemorrhage within 22 to 36 hours occurred in 1/71 and 0/60 (RR, infinity [95% CI, 0.06 to infinity]; P>0.999), respectively. Death at 90 days occurred in 2/71 and 2/60 (RR, 0.85 [95% CI, 0.06-12.58]; P>0.999), respectively. Conclusions- No difference in favorable outcome was seen between alteplase and control groups among patients with ischemic stroke with unknown time of onset. The safety of alteplase at 0.6 mg/kg was comparable to that of standard treatment. Early study termination precludes any definitive conclusions. Registration- URL: https://www.clinicaltrials.gov; Unique identifier: NCT02002325.

DOI： 10.1161/STROKEAHA.119.028127

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記述言語：日本語   掲載種別：研究論文（学術雑誌）  

Door to groin puncture time is one of the determinants of clinical outcome in patients treated with endovascular thrombectomy (EVT). We have recently initiated a protocol, direct transfer to angiographic site, for patients transferred from outside hospitals. In this retrospective study, we investigated whether our new protocol had succeeded in shortening the door to groin puncture time. Data on consecutive patients with an occlusion at internal carotid artery or middle cerebral artery treated with EVT transferred from outside hospital between July 2012 and December 2018 were studied. Good outcome was defined as modified Rankin Scale score (mRS) ≤1 at 3 months. Forty (46%) patients were directly transferred to angiographic suite, 27 (19%) were indirectly transferred after CT, and 20 (23%) were after MRI. Onset to admission time was similar among the 3 groups (P = 0.711), while door to groin puncture time was significantly shorter in patients directly transferred to angiographic suite compared to those after CT as well as MRI (median 22 [25%-75%, 16-31] minutes vs. 31 [27-40], vs. 84 [58-124], P < 0.001). The rates of reperfusion with ≥ Thrombolysis in Cerebral Infarction 2b were similar among the 3 groups (88% vs. 85% vs. 90%, P = 0.886). The incidences of symptomatic intracerebral hemorrhage were also similar as 8% vs. 4% vs. 5% (P = 0.796). At 3 months after stroke, 16 (40%) patients in the 11 (41%) in those after CT, and 9 (45%) in those after MRI had the good outcome (P = 0.931). Direct transfer to angiography suite can shorten the onset to groin puncture time with safety.

DOI： 10.5692/clinicalneurol.cn-001366

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記述言語：日本語   出版者・発行元：(一社)日本神経学会  

我々は、転帰改善のために血栓回収療法目的の転送受け入れを血管撮影室とする取り組みを開始した。血管撮影室へ直接転送群は、来院から穿刺までの時間が中央値で22分と、CT後入室群の31分やMRI後入室群の84分より短かった(P<0.001)。症候性頭蓋内出血の頻度は3群間で同等であった(P=0.796)。血管撮影室での転送受け入れは、安全に来院から穿刺までの時間を短縮させる可能性がある。(著者抄録)

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その他リンク： https://search-tp.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2020&ichushi_jid=J01550&link_issn=&doc_id=20200422420009&doc_link_id=1390848250106305920&url=https%3A%2F%2Fcir.nii.ac.jp%2Fcrid%2F1390848250106305920&type=CiNii&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00003_3.gif

記述言語：英語   掲載種別：研究論文（学術雑誌）  

As the goal of mechanical thrombectomy is shifting toward mTICI-3 rather than mTICI-2b, we sought to clarify the limitation of the effect of mTICI-3. A post-hoc analysis of a registry of large-vessel occlusion stroke from 46 centers was conducted. Among 2,420 registered patients, 725 patients with anterior circulation occlusion who achieved successful reperfusion were analyzed. We compared outcomes between patients with mTICI-3 and mTICI-2b, and investigated how the effect of mTICI-3 changed according to baseline characteristics and time course. The proportion of patients with favorable outcomes (mRS 0-2 at day 90) was higher among patients with mTICI-3 compared to those with mTICI-2b (adjusted OR, 2.10; 95% CI, 1.49-2.97). There was no heterogeneity in the effect of mTICI-3 with respect to age, neurological deficit, alteplase use, occluded vessels, or infarct size. mTICI-3 was associated with favorable outcomes when the puncture-to-reperfusion time was <80 minutes (adjusted OR, 2.28; 95% CI, 1.52-3.41), but not when the puncture-to-reperfusion time was ≥80 minutes. A significant heterogeneity was found in the effect of mTICI-3 reperfusion across the puncture-to-reperfusion time subgroups (P for interaction = 0.025). Until when operators should continue the procedure after mTICI-2b has been achieved, needs to be studied.

DOI： 10.1038/s41598-020-61748-y

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

OBJECTIVES: Cognitive assessment is not performed routinely in the acute stroke setting. We investigated factors associated with cognitive impairment and the differences between the Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA) scores in patients with acute stroke. METHODS: In this prospective study, 881 consecutive patients (median age, 73 years) with acute stroke were enrolled. Clinical characteristics, such as education, vascular risk factors, premorbid cognitive status using the Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE), and stroke severity, were assessed. Cognitive performance was measured using MMSE and MoCA within 5 days of stroke onset. RESULTS: Both MMSE and MoCA were feasible in 621 (70.5%) patients. Factors independently associated with nonfeasibility were age (odds ratio [OR]: 1.05; 95% confidence interval [CI]: 1.02-1.08), IQCODE score (OR: 1.02; 95%CI: 1.00-1.04), and National Institutes of Health Stroke Scale (NIHSS) score (OR, 1.16; 95%CI, 1.12-1.20). Impaired MoCA (with a cut-off <26/30) performance was observed in 544 of 621 (87.6%) patients. Factors independently associated with cognitive impairment were age (OR: 1.06; 95%CI: 1.03-1.10) and NIHSS score (OR: 1.34; 95%CI: 1.14-1.57). Eighty percent of patients with normal MMSE scores had an impaired MoCA score (MMSE-MoCA mismatch). The differences were highest in the visuospatial (94.8% versus 65.3%; P < .0001), recall (76.6% versus 35.6%; P < .0001), abstraction (82.5% versus 49.8%; P < .0001), and language (72.3% versus 65.9%; P < .0001) domains between the normal MMSE and MoCA group and MMSE-MoCA mismatch group. CONCLUSIONS: The MoCA can be particularly useful in patients with cognitive deficits undetectable on the MMSE in the acute stroke phase.

DOI： 10.1016/j.jstrokecerebrovasdis.2020.104688

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記述言語：英語  

DOI： 10.1016/j.jocn.2019.11.032

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記述言語：日本語   掲載種別：研究論文（学術雑誌）  

Epilepsy surgery for patients with drug-resistant epilepsy after anti-N-methyl-D-aspartate (NMDA) receptor encephalitis has been rarely reported. The present study reports two patients with anti-NMDA receptor encephalitis, who later underwent epilepsy surgery due to drug-resistant epilepsy. The patients had refractory status epilepticus in the acute phase. The cerebrospinal fluid was positive for anti-NMDA receptor antibodies. Systemic corticosteroid therapy and plasma exchange were effective. Seizure control, however, worsened over several months after discharge, and was refractory to antiepileptic drugs. They underwent palliative epilepsy surgery, and their seizure control improved. Epilepsy surgery should be considered in patients with drug-resistant epilepsy after anti-NMDA receptor encephalitis.

DOI： 10.5692/clinicalneurol.cn-001266

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記述言語：英語  

Here, we report a case involving a 67-year-old Japanese woman with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) associated with a novel in-frame complex rearrangement in the NOTCH3 gene. The patient had gradually developed cognitive impairment since the occurrence of an ischemic stroke at the age of 53 years. Her mother had a history of stroke and dementia. Fluid-attenuated inversion recovery magnetic resonance imaging of the brain showed hyperintense lesions in the bilateral temporal poles, external capsules, and periventricular white matter accompanied by multiple cerebral microbleeds on T2*-weighted gradient-echo imaging. A novel in-frame mutation (c.598_610delinsAGAACCC) resulting in the loss of Cys201 in the fifth epidermal growth factor-like repeat of NOTCH3 was identified; this led to a diagnosis of CADASIL. In summary, we report a novel pathogenic mutation (NOTCH3 c.598_610delinsAGAACCC; p.Pro200_Ser204delinsArgThrPro) associated with CADASIL. Further investigations should elucidate the genotype-phenotype correlations in patients with this in-frame complex rearrangement.

DOI： 10.1016/j.jstrokecerebrovasdis.2019.104482

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Mild encephalitis/encephalopathy with a reversible splenial lesion (MERS) is a clinicoradiological syndrome characterized by transient mild encephalopathy and magnetic resonance imaging (MRI) findings of a reversible lesion in the splenium of the corpus callosum (SCC). Patients with MERS generally present with central nervous system symptoms such as consciousness disturbance, headache, and seizure; adult-onset MERS with cerebellar ataxia is rare. A 53-year-old man was admitted to our hospital with fever of 1 week's duration, headache, neck stiffness, and gait disturbance. Neurological examination revealed bilateral intention tremor (predominantly affecting the right hand) and gait ataxia. Diffusion-weighted brain MRI showed a focal hyperintense lesion in the SCC. Cerebrospinal fluid analysis revealed elevated levels of mononuclear cells and proteins. Brain imaging with 123I-iofetamine single-photon emission computed tomography showed reduced cerebral blood flow in the left thalamus and right cerebellum. Several diseases, including cerebellar stroke and acute cerebellitis, develop as comorbidities in patients with acute cerebellar ataxia. This case suggests that MERS should be suspected in adults with cerebellar ataxia.

DOI： 10.1272/jnms.JNMS.2020_87-305

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Objectives: Clinical characteristics of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) include migraine, recurrent stroke, white matter lesions, and vascular dementia. CADASIL is one of the most common hereditary cerebral small vessel diseases. Clinical presentation of CADASIL varies and a racial gap may exist between the Asian and Caucasian populations. This is the first nationwide epidemiological survey which aimed to elucidate the clinical features of CADASIL in Japan. Moreover, the registration database of CADASIL was constructed. Methods: Subjects included CADASIL patients who visited the hospitals (totally 1,448 hospitals) certified by the Japanese Society of Neurology and/or Japan Stroke Society in 2016. This study consisted of a two-step survey; patients with CADASIL were identified genetically by the first questionnaire, and their clinical features were assessed by the second questionnaire. Selected 6 hospitals registered the data of all CADASIL patients using a Research Electronic Data Capture (REDCap) system for the second questionnaire. Results: Based on the criteria, 88 patients (50 male and 38 female) with CADASIL were enrolled. The mean age of symptom onset was 49.5 years. Sixteen (18.2%) patients had an elderly onset (>60 years). Thirteen patients (13.6%) had history of migraine with aura and 33 patients (37.5%) had vascular risk factor(s). From among the 86 patients who were examined using magnetic resonance imaging, abnormal deep white matter lesions were detected in 85 patients (98.8%), WMLs extending to anterior temporal pole in 73 patients (84.9%), and cerebral microbleeds in 41 patients (47.7%). Anti-platelet therapy was received by 65 patients (73.9%). Thirty-eight patients (43.2%) underwent treatment with lomerizine hydrochloride. Thirty-four different mutations of NOTCH3 were found in exons 2, 3, 4, 5, 6, 8, 11, 14, and 19. Most of the mutations existed in exon 4 (n = 44, 60.3%). The prevalence rate of CADASIL was 1.20 to 3.58 per 100,000 adults in Japan. Conclusion: This questionnaire-based study revealed clinical features and treatment status in Japanese CADASIL patient, although it may not be an exhaustive search. We have constructed the REDCap database for these CADASIL patients.

DOI： 10.3389/fnagi.2020.00216

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1016/j.jjcc.2019.06.002

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1016/j.ensci.2019.100210

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

OBJECTIVES: The management of atrial fibrillation and deep venous thrombosis has evolved with the development of direct oral anticoagulants (DOAC), and oral anticoagulant (OAC) might influence the development or clinical course in both ischemic and hemorrhagic stroke. However, detailed data on the differences between the effects of the prior prescription of warfarin and DOAC on the clinical characteristics, neuroradiologic findings, and outcome of stroke are limited. DESIGN: The prospective analysis of stroke patients taking anticoagulants (PASTA) registry study is an observational, multicenter, prospective registry of stroke (ischemic stroke, transient ischemic attack, and intracerebral hemorrhage) patients receiving OAC in Japan. This study is designed to collect data on clinical background characteristics, drug adherence, drug dosage, neurological severity at admission and discharge, infarct or hematoma size, acute therapy including recanalization therapy or reverse drug therapy, and timing of OAC re-initiation. Patient enrollment started in April 2016 and the target patient number is 1000 patients. CONCLUSIONS: The PASTA prospective registry should identify the status of stroke patients taking OAC in the current clinical practice in Japan.

DOI： 10.1016/j.jstrokecerebrovasdis.2019.104456

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記述言語：日本語   出版者・発行元：(NPO)日本脳神経血管内治療学会  

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記述言語：日本語   出版者・発行元：(NPO)日本脳神経血管内治療学会  

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記述言語：日本語   出版者・発行元：(一社)日本神経学会  

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記述言語：日本語   出版者・発行元：(NPO)日本脳神経血管内治療学会  

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記述言語：日本語   出版者・発行元：(NPO)日本脳神経血管内治療学会  

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記述言語：日本語   出版者・発行元：(NPO)日本脳神経血管内治療学会  

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記述言語：日本語   出版者・発行元：(NPO)日本脳神経血管内治療学会  

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記述言語：日本語   出版者・発行元：(NPO)日本脳神経血管内治療学会  

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記述言語：日本語   出版者・発行元：(NPO)日本脳神経血管内治療学会  

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記述言語：日本語   出版者・発行元：(NPO)日本脳神経血管内治療学会  

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記述言語：日本語   出版者・発行元：(NPO)日本脳神経血管内治療学会  

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記述言語：日本語   出版者・発行元：(NPO)日本脳神経血管内治療学会  

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記述言語：日本語   出版者・発行元：(NPO)日本脳神経血管内治療学会  

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記述言語：日本語   出版者・発行元：(NPO)日本脳神経血管内治療学会  

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記述言語：日本語   出版者・発行元：(NPO)日本脳神経血管内治療学会  

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記述言語：日本語   出版者・発行元：(一社)日本神経学会  

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記述言語：日本語   出版者・発行元：(一社)日本神経学会  

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記述言語：日本語   出版者・発行元：日本医科大学医学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

RATIONALE: Bridging therapy with endovascular therapy (EVT) and intravenous thrombolysis (IVT) has been reported to improve outcomes for acute stroke patients with large-vessel occlusion in the anterior circulation. While the IVT may increase the reperfusion rate, the risk of hemorrhagic complications increases. Whether EVT without IVT (direct EVT) is equally effective as bridging therapy in acute stroke remains unclear. AIM: This randomized study of endovascular therapy with versus without intravenous tissue plasminogen activator for acute stroke with ICA and M1 occlusion aims to clarify the efficacy and safety of direct EVT compared with bridging therapy. METHODS AND DESIGN: This is an investigator-initiated, multicenter, prospective, randomized, open-treatment, blinded-endpoint clinical trial. The target patient number is 200, comprising 100 patients receiving direct EVT and 100 receiving bridging therapy. STUDY OUTCOME: The primary efficacy endpoint is a modified Rankin Scale score of 0-2 at 90 days. Safety outcome measures are any intracranial hemorrhage at 24 h. DISCUSSION: This trial may help determine whether direct EVT should be recommended as a routine clinical strategy for ischemic stroke patients within 4.5 h from onset. Direct EVT would then become the choice of therapy in stroke centers with endovascular facilities. TRIAL REGISTRATION: UMIN000021488.

DOI： 10.1177/1747493019840932

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記述言語：日本語   出版者・発行元：(一社)日本神経治療学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.4103/1673-5374.255964

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掲載種別：研究論文（学術雑誌）  

Background: National institutes of Health Stroke Scale (NIHSS) score and the presence of successful recanalization are crucial determinants of clinical outcome in patients with major artery occlusion. However, it is unknown whether successful recanalization rate after endovascular therapy (EVT) depends on NIHSS score. Methods: From our prospective EVT registry, data on patients with an occlusion at the internal carotid artery or middle cerebral artery were analyzed. Successful recanalization was judged as positive when reperfusion of the thrombolysis in cerebral infarction (TICI) scale ≥2b was observed. Successful recanalization rate was also evaluated based on the NIHSS score subgroups: 0–8, 9–16, 17–24, and >24. Multivariate regression analysis was used to evaluate the impact of NIHSS score on successful recanalization. Results: We studied 183 patients (age 76 [68–83], male 110 [60%], NIHSS score 19 [14–24]). One hundred and forty-six (80%) patients had the successful recanalization. Patients achieved the recanalization had lower NIHSS score as 18 (12−23), contrary those failed it had higher NIHSS score as 24 (20–27) (p < .001). Successful recanalization rate was correlated to the NIHSS score grade; 100% in the NIHSS 0–8 group, 88% in 9–16, 81% in 17–24, and only 60% in >24 (p < .001). Multivariate regression analysis showed NIHSS score was an independent parameter of recanalization (odds ratio 0.905 [95%CI 0.837–0.979], p = .013). Conclusion: NIHSS score may serve as a predictor of successful recanalization. Recanalization is relatively easier in mild stroke than in those with severe stroke.

DOI： 10.1016/j.jns.2019.06.033

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: National institutes of Health Stroke Scale (NIHSS) score and the presence of successful recanalization are crucial determinants of clinical outcome in patients with major artery occlusion. However, it is unknown whether successful recanalization rate after endovascular therapy (EVT) depends on NIHSS score. METHODS: From our prospective EVT registry, data on patients with an occlusion at the internal carotid artery or middle cerebral artery were analyzed. Successful recanalization was judged as positive when reperfusion of the thrombolysis in cerebral infarction (TICI) scale ≥2b was observed. Successful recanalization rate was also evaluated based on the NIHSS score subgroups: 0-8, 9-16, 17-24, and >24. Multivariate regression analysis was used to evaluate the impact of NIHSS score on successful recanalization. RESULTS: We studied 183 patients (age 76 [68-83], male 110 [60%], NIHSS score 19 [14-24]). One hundred and forty-six (80%) patients had the successful recanalization. Patients achieved the recanalization had lower NIHSS score as 18 (12-23), contrary those failed it had higher NIHSS score as 24 (20-27) (p < .001). Successful recanalization rate was correlated to the NIHSS score grade; 100% in the NIHSS 0-8 group, 88% in 9-16, 81% in 17-24, and only 60% in >24 (p < .001). Multivariate regression analysis showed NIHSS score was an independent parameter of recanalization (odds ratio 0.905 [95%CI 0.837-0.979], p = .013). CONCLUSION: NIHSS score may serve as a predictor of successful recanalization. Recanalization is relatively easier in mild stroke than in those with severe stroke.

DOI： 10.1016/j.jns.2019.06.033

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Background The aim of the present study was to investigate the efficacy and safety of antiplatelet (aspirin plus cilostazol) dual therapy for patients with noncardioembolic stroke within 48 hours of symptom onset. Methods and Results The ADS (Acute Aspirin Plus Cilostazol Dual Therapy for Non-Cardiogenic Stroke Patients Within 48 Hours of Symptom Onset ) study is an investigator-initiated, prospective, multicenter (34 hospitals in Japan), randomized, open-label, and aspirin-controlled trial. Acute stroke patients with noncardioembolic stroke within 48 hours of onset were studied. The subjects were randomly allocated to combination therapy with aspirin 81 to 200 mg plus cilostazol 200 mg (dual group) and single therapy with aspirin 81 to 200 mg (aspirin group) for 14 days. After the 14 days, all patients took the cilostazol 200 mg for 3 months. A primary efficacy outcome was defined as any one of the following occurring (neurological deterioration, symptomatic stroke recurrence, or transient ischemic attack) within 14 days. A primary safety outcome included intracerebral hemorrhage and subarachnoid hemorrhage. Between May 2011 and June 2017, 1201 patients (796 [66%] men; median age, 69 [61-77] years) randomized 1:1 to either the dual group or the aspirin group were analyzed. Initial National Institutes of Health Stroke Scale score was 2 (1-4) in both groups (P=0.830). A primary efficacy outcome was observed in 11% in the dual group and 11% in the aspirin group (P=0.853). A primary safety outcome occurred in 2 (0.3%) in the dual group and in 1 (0.2%) in the aspirin group (P=0.624). Conclusions Dual antiplatelet therapy using cilostazol and aspirin was safe but did not reduce the rate of short-term neurological worsening. Clinical Trial Registration URL: umin.ac.jp/ctr/index/htm. Unique identifier: UMIN000004950.

DOI： 10.1161/JAHA.119.012652

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

OBJECTIVE: Dopamine transporter (DAT) imaging such as 123I-ioflupane (123I-FP-CIT) SPECT is a useful tool for the diagnosis of parkinsonism and dementia. The Southampton method is the quantitative method for evaluating 123I-FP-CIT SPECT and is less affected by the partial volume effect of the striatum. The method may be vulnerable to contamination by low-uptake areas of cerebrospinal fluid in whole brain, and the threshold of voxel value (threshold method, TM) was developed to correct the contamination. The purpose of this study is to evaluate the TM in the patients with neurological disease. METHODS: We studied 99 subjects, including 39 patients with Alzheimer's disease (AD), 15 patients with Parkinson's disease (PD) and 10 patients with dementia with Lewy bodies (DLB). Each subject had undergone 123I-FP-CIT SPECT. We calculated the SBR with and without the TM. The SBR laterality was assessed using the asymmetry index (AI). We investigated the relationship between the SBR change with TM and brain atrophy, which were assessed using Evans index (EI), sylvian index (SI) and cerebral atrophy index (CAI). Cutoff value for EI was 0.3, and cutoff values for SI and CAI were the first quartile, respectively. RESULTS: The SBR with TM was 0.53 percentage points lower than the SBR without TM overall (p < 0.01). Positive and negative reversal of AI increased with age. The rate of the SBR change with TM was tended to be lower in groups with brain atrophy. The number of voxels excluded by TM in striatal volumes of interest (VOIs) was larger with high groups for EI, SI and CAI than in low groups. The number of voxels excluded using TM in reference VOIs was related to SI. CONCLUSIONS: The SBR was decreased using TM. The effect of TM on the SBR tended to be small in the subjects with severe brain atrophy. The effect of brain atrophy in the TM is larger in the striatal VOIs than in the reference VOIs. Even if quantitative analyses are available, visual assessment of 123I-FP-CIT SPECT is essential for diagnosis.

DOI： 10.1007/s12149-019-01367-4

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記述言語：英語  

Here, we report the case of a 27-year-old woman with tuberous sclerosis complex who underwent successful endovascular intervention for cerebral venous thrombosis at the superior sagittal sinus. She had protein S deficiency and a long-term history of anemia caused by menorrhagia from uterine fibroids, possibly leading to a hypercoagulable state. Cerebral venous sinus thrombosis accounts for ~0.5-1% of all strokes. Several cases of venous thrombosis in patients with tuberous sclerosis complex and protein S or protein C deficiency have been reported, but further studies are needed to identify whether an association of this rare combination may be explained.

DOI： 10.1093/omcr/omz060

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記述言語：日本語   出版者・発行元：Movement Disorder Society of Japan (MDSJ)  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Although dual antiplatelet therapy with aspirin and clopidogrel reduces early recurrence of ischaemic stroke, with long-term use this type of therapy is no longer effective and the risk of bleeding increases. Given that cilostazol prevents stroke recurrence without increasing the incidence of serious bleeding compared with aspirin, we aimed to establish whether dual antiplatelet therapy involving cilostazol is safe and appropriate for long-term use. METHODS: In a multicentre, open-label, randomised controlled trial across 292 hospitals in Japan, patients with high-risk non-cardioembolic ischaemic stroke identified on MRI were randomly assigned to two groups in a 1:1 ratio to receive monotherapy with either oral aspirin (81 or 100 mg, once per day) or clopidogrel (50 or 75 mg, once per day) alone, or a combination of cilostazol (100 mg, twice per day) with aspirin or clopidogrel. Randomisation was done centrally (using block randomisation with a block size of six per each participating hospital) through a web-based registration system and was done by EPS Corporation. The patients were required to have at least 50% stenosis of a major intracranial or extracranial artery or two or more of the vascular risk factors. Trial medication was continued for half a year or longer, for a maximum of 3·5 years. The primary efficacy outcome was the rate of first recurrence of symptomatic ischaemic stroke. Safety outcomes were severe or life-threatening bleeding; any adverse events; serious adverse events; and any bleeding events. Efficacy analyses were done in the intention-to-treat population and safety analyses were done in the as-treated population. This trial was registered with ClinicalTrials.gov (number NCT01995370) and UMIN Clinical Trials Registry (number 000012180). FINDINGS: Participants were recruited from Dec 13, 2013, to March 31, 2017. 932 patients assigned to the dual therapy group and 947 patients assigned to the monotherapy group were included in the intention-to-treat analysis. The trial was stopped after the enrolment of 1884 patients of an anticipated 4000 patients because of the delay in recruitment. Ischaemic stroke recurred in 29 (3%) of 932 patients (annualised rate 2·2%) on dual therapy including cilostazol and 64 (7%) of 947 patients (annualised rate 4·5%) on monotherapy during a median 1·4 years follow-up (hazard ratio [HR] 0·49, 95% CI 0·31-0·76, p=0·0010). Severe or life-threatening bleeding occurred in eight patients (annualised rate 0·6%) on dual therapy and 13 patients (annualised rate 0·9%) on monotherapy (HR 0·66, 95% CI 0·27-1·60, p=0·35). Occurrence of any type of adverse event was similar between the groups (255 [28%] of 910 patients in the dual therapy group vs 219 [24%] of 921 patients in the monotherapy group); as was occurrence of serious adverse events (87 [10%] vs 142 [15%]) and bleeding events (38 [4%] vs 33 [4%]). Gastrointestinal bleeding, which affected nine (<1%) of 910 patients in the monotherapy group and nine (<1%) of 921 patients in the dual therapy group, was the most common type of bleeding. INTERPRETATION: The combination of cilostazol with aspirin or clopidogrel had a reduced incidence of ischaemic stroke recurrence and a similar risk of severe or life-threatening bleeding compared with treatment with aspirin or clopidogrel alone in patients at high risk for recurrent ischaemic stroke. FUNDING: Otsuka Pharmaceutical.

DOI： 10.1016/S1474-4422(19)30148-6

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Atrial fibrillation (AF) is the leading cause of cardioembolic stroke (CES), and patients with stroke and AF are frequently assumed to have CES. However, strokes presumably due to atherosclerotic pathophysiologies in large or small vessels can also occur in patients with AF. The aims of the present study were to clarify the prevalence of and factors related to a non-cardioembolic etiology in acute stroke patients with AF. METHODS: From March 2011 through May 2017, consecutive acute ischemic stroke patients with AF were retrospectively recruited. The concomitant presence of non-cardioembolic features (small vessel occlusion [SVO] or large artery atherosclerosis [LAA]) on imaging was evaluated. The frequency of and factors associated with co-existing SVO/LAA features were assessed. RESULTS: A total of 560 consecutive patients with AF and acute stroke (237 women; median age 78 [IQR 71-85] years; NIHSS score 9 [3-20]) were enrolled. Of these, 42 (7.5%) had co-existing SVO/LAA features. Multivariable logistic regression analysis showed that the brain natriuretic peptide level (BNP, OR 0.78, p = .030 per 100 pg/mL increase) was independently and negatively associated with co-existing SVO/LAA features and receiver operating characteristic curve analysis revealed the practical cut-off BNP value was 130 pg/mL (sensitivity 54% and specificity 68%). CONCLUSION: SVO/LAA features were found in 7.5% of acute stroke patients with AF. A relatively low BNP level on admission was independently associated with co-existing SVO/LAA features. Thorough examination for a more appropriate etiology may be particularly necessary in acute stroke patients with AF and a relatively low BNP level.

DOI： 10.1016/j.jns.2019.03.031

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Anticoagulant therapy often requires temporary interruption. Nevertheless, the frequency and clinical characteristics of stroke patients who develop stroke during anticoagulant interruption are not fully known. METHODS: From March 2011 through May 2017, consecutive acute ischemic stroke patients with AF who were admitted to our stroke unit were retrospectively recruited. Patients who developed ischemic stroke during anticoagulant interruption were defined as those who developed ischemic stroke within 30 days from anticoagulant interruption. The frequency and clinical characteristics of patients during anticoagulant interruption were analyzed. RESULTS: A total of 561 patients with AF and acute ischemic stroke (237 women; median age 78 [IQR 71-85] years) were admitted during the study period. Of these, 21 (3.7%, 12 patients discontinued vitamin K antagonist [VKA] and 9 discontinued direct oral anticoagulants [DOACs]) patients were admitted during the period of anticoagulant interruption. Severity and functional outcomes in stroke patients during anticoagulant interruption were not different from those without anticoagulant treatment. The number of days between anticoagulant interruption and stroke onset was shorter in patients who discontinued DOACs (3 [3-5] days) than in those who discontinuedVKAs (10 [7-20] days, p = .004). The major reason for interruption was planning of invasive procedures (52%). Guideline deviations were suspected in 82% of such cases. CONCLUSION: Patients developing stroke during anticoagulant interruption accounted for 3.7% of stroke patients with AF. Strokes occurred relatively early after interruption, especially in patients who discontinued DOACs. Guideline deviations was frequent.

DOI： 10.1016/j.jns.2019.03.018

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

OBJECTIVE: We investigated the precise clinical and radiologic characteristics of intracerebral hemorrhage associated with direct oral anticoagulant use. METHODS: Patients with acute spontaneous intracerebral hemorrhage admitted to our department from September 2014 to November 2017 were retrospectively analyzed. Clinical and neuroradiological characteristics of patients with direct oral anticoagulant-related intracerebral hemorrhage, and effects of prior treatment on the severity at admission and on outcome at discharge were assessed. RESULTS: Of the 301 enrolled patients (103 women; median age 68 years), 261 received no oral anticoagulants (86.8%), 20 received warfarin (6.6%), and 20 received direct oral anticoagulants (DOACs) (6.6%). Median initial National Institutes of Health Stroke Scale scores differed significantly among the groups (P = .0283). Systolic blood pressure (P = .0031) and estimated glomerular filtration rate (P = .0019) were significantly lower in the oral anticoagulant-related intracerebral hemorrhage group than in other groups. Total small vessel disease scores were significantly higher in the oral anticoagulant-related intracerebral hemorrhage group than in the warfarin group (P = .0413). Multivariate analysis revealed that prior oral anticoagulant treatment (odds ratio: 0.21, 95% confidence interval: 0.05-0.96, P = .0445) was independently negatively associated with moderate-to-severe neurological severity (stroke scale score ≥10) after adjusting for intracerebral hemorrhage location and various risk factors. There were significant differences in hematoma volume in the basal ganglia (P = .0366). CONCLUSIONS: DOAC-related intracerebral hemorrhage may occur particularly in patients with a high risk of bleeding; however, they had a milder initial neurological severity than those with warfarin-related intracerebral hemorrhage, possibly due to relatively smaller hematoma volume, especially in the basal ganglia.

DOI： 10.1016/j.jstrokecerebrovasdis.2018.12.013

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記述言語：日本語   出版者・発行元：(一社)日本神経学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1016/j.ensci.2018.12.001

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Because the efficacy and safety of anticoagulant therapy in patients with acute intracerebral hemorrhage (ICH) are not fully known, present study aimed to elucidate the current status and the safety of anticoagulant therapy, mainly direct oral anticoagulants (DOACs), for acute ICH and anticoagulant-indicated patients. Methods and Results: From September 2014 through March 2017, consecutive patients with acute (<7 days from onset), spontaneous ICH were retrospectively enrolled from a prospective registry. Whether to start anticoagulation was at the attending physicians' discretion, and thromboembolic or hemorrhagic events during hospitalization were analyzed. A total of 236 patients (80 women [34%]; median age 69 [interquartile range 61-79] years; National Institutes of Health stroke scale score 7 [3-16]) were enrolled. Of them, 47 patients (20%) had an indication for anticoagulant therapy (33 had atrial fibrillation, 14 developed deep vein thrombosis), and 41 of 47 patients (87%) were actually treated with anticoagulant therapy (DOACs were used in 34 patients) after a median of 7 days from ICH onset. There was neither hematoma expansion nor excessive hemorrhagic complications during hospitalization after starting anticoagulant therapy. CONCLUSIONS: Anticoagulant therapy was conducted for approximately 90% of anticoagulation-indicated patients after a median of 7 days from ICH onset. The predominant anticoagulant medications were DOACs. Anticoagulant therapy started from the acute phase of ICH should be safe.

DOI： 10.1253/circj.CJ-18-0938

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記述言語：英語   出版者・発行元：Elsevier BV  

DOI： 10.1016/j.biopha.2018.09.084

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その他リンク： https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-26293328/

記述言語：日本語   出版者・発行元：(一社)日本神経学会  

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記述言語：日本語   出版者・発行元：(一社)日本神経学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND AND PURPOSE: The association between thyroid hormone levels and long-term clinical outcome in patients with acute stroke has not yet been thoroughly studied. The purpose of the present study was to test the hypothesis that thyroid hormone levels are associated with 3-month functional outcome and mortality after acute stroke. METHODS: We retrospectively analyzed 702 consecutive patients with acute stroke (251 women; median age, 73 years) who were admitted to our department. General blood tests, including thyroid stimulating hormone (TSH), free triiodothyronine (FT3), and free thyroxine (FT4), were performed on admission. Neurological severity was evaluated using National Institutes of Health Stroke Scale (NIHSS) scores on admission and modified Rankin Scale (mRS) scores at 3 months after stroke onset. Poor outcome was defined as an mRS score of 3-5 or death. The impact of thyroid function on 3-month outcome was evaluated using multiple logistic regression analysis. RESULTS: Poor functional outcome was observed in 295 patients (42.0%). Age (P < .0001), female sex (P < .0001), admission NIHSS score (P < .0001), smoking (P = .0026), arterial fibrillation (P = .0002), preadmission mRS (P < .0001), estimated glomerular filtration rate (P = .0307), and ischemic heart disease (P = .0285) were significantly associated with poor functional outcome, but no relationship between FT4, TSH, and poor functional outcome was found. A multivariate logistic regression analysis showed that low FT3 values (<2.00 pg/mL) were independently associated with poor functional outcome (odds ratio [OR], 3.16; 95% confidence interval [CI], 1.60-6.24) and mortality (OR, 2.55; 95% CI, 1.33-4.91) at 3 months after stroke onset. CONCLUSIONS: Our data suggest that a low FT3 value upon admission is associated with a poor 3-month functional outcome and mortality in patients with acute stroke.

DOI： 10.1016/j.jstrokecerebrovasdis.2018.06.009

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: This study investigated changes in anticoagulant use, treatment, and functional outcomes in acute ischemic stroke (AIS) patients with non-valvular atrial fibrillation (NVAF) over a 6-year period. Methods and Results: Patients with AIS and NVAF admitted to our department from April 2011 to March 2017 were analyzed retrospectively. Patients were divided into 3 groups based on the time of the initial visit (Periods 1-3, corresponding to April 2011-March 2013, April 2013-March 2015, and April 2015-March 2017, respectively). Associations between prescribed medication prior to event and stroke severity, reperfusion therapy, and outcomes were assessed. There was no significant change in the rate of insufficient warfarin and inappropriately lowered doses of direct oral anticoagulant (DOAC) treatment over time. The number of patients receiving prior DOAC treatment increased, but neurological severity on admission was milder than in the other 2 groups. The rate of reperfusion therapy increased from 19.9% (Period 1) to 42.7% (Period 3) for moderate-to-severe stroke patients. Multivariate logistic regression analysis revealed that reperfusion therapy was independently positively associated with good functional outcomes, but negatively associated with mortality (odds ratios [95% confidence intervals] 7.14 [3.34-15.29] and 0.13 [0.008-0.69], respectively). CONCLUSIONS: Inappropriate anticoagulant use for stroke patients with NVAF did not decrease over time. An increase in reperfusion therapy was a strong factor in improved functional outcomes and mortality.

DOI： 10.1253/circj.CJ-18-0561

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記述言語：英語   出版者・発行元：Elsevier BV  

DOI： 10.1016/j.omtm.2018.07.009

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その他リンク： https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-26293328/

記述言語：英語   掲載種別：研究論文（学術雑誌）  

Background The aims of the present study were to investigate the relationships between prior direct oral anticoagulant ( DOAC ) therapy and infarct volume and the site of arterial occlusion in patients with acute ischemic stroke and non-valvular atrial fibrillation. Methods and Results From March 2011 through November 2016, consecutive patients with acute ischemic stroke in the middle cerebral artery territory and non-valvular atrial fibrillation were recruited. The infarct volume was assessed semi-automatically using initial diffusion-weighted imaging, and the arterial occlusion site was evaluated on magnetic resonance angiography. The effect of prior DOAC treatment on the site of arterial occlusion was assessed by multivariate ordinal logistic regression analysis. A total of 330 patients (149 women; median age 79 [quartiles 71-86] years; median National Institutes of Health Stroke Scale score 11 [4-21]) were enrolled. Of these, 239 were on no anticoagulant, 40 were undertreated with a vitamin K antagonist ( VKA ), 22 were sufficiently treated with VKA ( PT - INR ≥1.6), and 29 were on a DOAC before the acute ischemic stroke. The infarct volume on admission differed among the groups (median 14.5 [2.0-59.8] cm3 in patients with no anticoagulation, 24.8 [2.1-63.0] in undertreated VKA , 1.3 [0.3-13.5] in sufficient VKA , and 2.3 [0.5-21.0] in DOAC , P=0.001). Multivariate analysis showed that prior DOAC treatment was independently and negatively associated with more proximal artery occlusion (odds ratio [OR] 0.34, P=0.015), compared with no anticoagulant. Conclusions DOAC treatment before the event was associated with smaller infarct volume and decreased risk of greater proximal artery occlusion in acute ischemic stroke patients with non-valvular atrial fibrillation, compared with no anticoagulation.

DOI： 10.1161/JAHA.118.009507

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Background and Purpose- The strong evidence of endovascular therapy in acute ischemic stroke patients with large vessel occlusion (LVO) is revealed. Such patients are required to direct transport to the hospital capable of endovascular therapy. There are several prehospital scales available for paramedics to predict LVO. However, they are time consuming, and several of them include factors caused by other types than LVO. Therefore, we need a fast, simple, and reliable prehospital scale for LVO. Methods- We developed a new prehospital stroke scale, emergent large vessel occlusion (ELVO) screen, for paramedics to predict LVO. The study was prospectively performed by multistroke centers. When paramedics referred to stroke center to accept suspected stroke patients, we obtain the following information over the telephone. ELVO screen was designed focusing on cortical symptoms: 1 observation; presence of eye deviation and 2 questions; paramedics show glasses, what is this? and paramedics show 4 fingers, how many fingers are there? If the presence of eye deviation or ≥1 of the 2 items were incorrect, ELVO screen was identified as positive. We evaluated between results of ELVO screen and presence of LVO on magnetic resonance angiography at hospital arrival. Results- A total of 413 patients (age, 74±13 years; men, 234 [57%]) were enrolled. Diagnosis was ischemic stroke, 271 (66%); brain hemorrhage 73 (18%); subarachnoid hemorrhage, 7 (2%); and not stroke, 62 (15%). One hundred fourteen patients had LVO (internal carotid artery, 33 [29%]; M1, 52 [46%]; M2, 21 [18%]; basilar artery, 5 [4%]; P1, 3 [3%]). Sensitively, specificity, positive predictive value, negative predictive value, and accuracy for ELVO screen to predict LVO were 85%, 72%, 54%, 93% and 76%, respectively. Among 233 patients with negative ELVO screen, only 17 (7%) had LVO, which indicated to be an ideal scale to avoid missing endovascular therapy. Conclusions- The ELVO screen is a simple, fast, and reliable prehospital scale for paramedics to identify stroke patients with LVO for whom endovascular therapy is an effective treatment.

DOI： 10.1161/STROKEAHA.118.022107

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記述言語：日本語   掲載種別：研究論文（学術雑誌）  

Rapid adaption of endovascular thrombectomy (EVT) is essential for patients with large arterial occlusion (LAO). Although patients transferred need longer transportation, they have an advantage of preadmission diagnosis regarding arterial occlusion. The aim of the present study is to evaluate whether optimizing the assessment at comprehensive center for patients transferred may improve the clinical outcome after EVT. Data on consecutive patients treated with EVT between September 2014 and May 2017 were studied. Generally, we have two distinct protocols for EVT candidates: 1) the transfer group, patients are directly taken to the CT and escorted to the angiography room; and 2) the direct group, patients receive the routine emergent evaluation and examined with MRI/MRA. Good outcome was defined as modified Rankin Scale score ≤1 at 3 months. Thirty-one (29%) patients were classified into the transfer group and the 77 (71%) were into the direct group. Although the onset to door time was longer in the transfer group (175 [137-275] min. vs. 76 [51-260] min, P = 0.001), the rate of good outcome was similar between the 2 groups (41% vs. 25%, P = 0.205). By multivariate regression analysis, the onset to reperfusion time was the independent factor (odds ratio 0.982, 95%CI: 0.967-0.998, P = 0.026) associated with good outcome, while transfer itself was not the independent parameter (odds ratio 0.732, 95%CI: 0.125-4.291, P = 0.730). Regarding time parameters, door to picture time (11 [7-24] min vs. 27 [21-39] min., P < 0.001) and picture to puncture time (27 [18-60] min. vs. 54 [39-78] min, P < 0.001) were shorter in the transfer group. Thus, the onset to puncture time (234 [177-299] min. vs. 170 [125-367] min, P = 0.063) and the onset to reperfusion time (271 [208-352] min. vs. 237 [159-382] min., P = 0.183) were similar between the 2 groups. Shortening the initial evaluation at comprehensive stroke center can provide a good outcome for patients transferred.

DOI： 10.5692/clinicalneurol.cn-001181

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Perampanel (PER), a noncompetitive α-amino-3-hydroxy-5-methyl-4-isoxazole propionate receptor antagonist, clinically used for seizure control, has been reported to exert neuroprotective effects in experimental models of neurodegenerative diseases. However, few studies have investigated the therapeutic effects of PER in brain injury including stroke. Our aim was to investigate the neuroprotective potential of PER using a rat transient middle cerebral artery occlusion (MCAO) model. Sprague-Dawley rats underwent 90-min MCAO followed by intraperitoneal PER administration at a dose of 1.5 mg/kg. Infarct volumes, neurological deficits, and immunological analyses were performed at 7 days after MCAO. PER significantly reduced infarct volumes (p < 0.05) and improved motor function (p < 0.05) compared with vehicle. Immunological analysis showed that PER significantly inhibited microglial activation, pro-inflammatory cytokine expression, and oxidative stress compared with vehicle. Moreover, PER suppressed neurodegeneration in the cortical ischemic boundary zone, via downregulation of Bcl-2-associated x and upregulation of Bcl-extra-large with Akt activation. In addition, post-stroke secondary neuronal damage and cognitive impairments, using the Y-maze test, were assessed 30 days after MCAO. PER significantly improved spatial working memory, which was accompanied by hippocampal CA1 neuronal loss and cortical thinning, compared with vehicle. These results indicate that PER attenuates infarct volumes and motor function deficits possibly through its anti-inflammatory, antioxidant, and anti-apoptotic activities, mediated via activation of phosphatidylinositol 3-kinase (PI3K)/Akt pathways in the acute ischemic phase, and further ameliorates post-stroke cognitive impairments via the suppression of secondary neuronal damage in the chronic ischemic phase.

DOI： 10.1016/j.neuroscience.2018.06.043

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：W.B. Saunders  

Background and Purpose: Anemia upon hospital admission is a known predictor of poor functional outcomes in patients with acute cerebral infarction. However, it remains unclear whether reductions in hemoglobin levels during hospitalization influence stroke outcomes. We investigated the association between in-hospital decline in hemoglobin and poor outcomes. Materials and Methods: We retrospectively analyzed data from 480 consecutive patients who had experienced acute cerebral infarction and presented without anemia between January 2012 and March 2015. Decline in hemoglobin was taken as the difference between hemoglobin levels upon admission and nadir hemoglobin. Poor outcome was defined as a modified Rankin Scale score 3-6. A multivariate analysis of the relationship between decline in hemoglobin and poor outcome at discharge was conducted for various patient characteristics. Results: The mean hemoglobin level at admission was 14.3 ± 1.3 g/dL, whereas the mean nadir hemoglobin value was 13.1 ± 1.9 g/dL, with a mean decline in hemoglobin of 1.3 ± 1.5 g/dL. In patients with poor outcomes, mean decline in hemoglobin was significantly reduced to 3.1 g/dL (P &lt
.001). The optimal cutoff decline in hemoglobin required to distinguish a poor outcome was 1.5 g/dL whereas the sensitivity and specificity were 62% and 82.3%, respectively, with an area under the curve of .77 (P &lt
.0001). A decline in hemoglobin below 1.5 g/dL was found to be an independent predictor of poor outcome (odds ratio: 2.10
confidence interval: 1.10-3.99
P = .023). Conclusion: Decline in hemoglobin in patients hospitalized with acute stroke may be associated with poor outcome.

DOI： 10.1016/j.jstrokecerebrovasdis.2018.01.026

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Elsevier B.V.  

Introduction: Magnetic resonance imaging (MRI) has recently emerged as a first-line tool for investigating acute stroke. However, MRI requires long scan times, which could be detrimental for severe stroke patients with a large intracerebral hemorrhage (ICH). MRI scout images, which are taken prior to a study to determine the range of subsequent images, can be used to rapidly screen the whole brain. We examined whether MRI scout imaging can detect ICHs observed by computed tomography (CT). Methods: Between September 2014 and March 2016, consecutive acute ICH patients who underwent both MRI scout and CT imaging in the acute setting were studied. ICHs on MRI scout images were defined as space-occupying lesions. Two neurologists independently assessed the scout images. We investigated whether ICHs on CT scans can be detected on MRI scout images and the characteristics of ICHs not detected by MRI scout images. Results: One hundred and forty-eight ICH patients (median age, 68 [interquartile range, 59–77] years
99 [67%] males
median National Institutes of Health Stroke Scale score, 11 [4–17]) were enrolled. Among these, 138 (93%) patients were diagnosed as having ICH by MRI scout imaging (positive group), and 10 (7%) patients were not (negative group). The bleeding volume was 9.3 [4.5–22.4] ml in the positive group and 1.0 [0.4–2.0] ml in the negative group (p &lt
.001). The cut-off value of bleeding volume calculated from the receiver operating characteristic curve was 2.0 ml. Regarding ICH lesions, 4 (44%) of the 9 pontine hemorrhages were detected on MRI scout images, whereas 134 (96%) of the 139 other hemorrhages were diagnosed (p &lt
.001). Conclusions: We diagnosed &gt
90% of ICHs using MRI scout images. Low levels of ICH and pontine hemorrhaging might be difficult to detect using MRI scout imaging.

DOI： 10.1016/j.jns.2018.01.041

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記述言語：日本語   出版者・発行元：(一社)日本神経学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Dr. Dietrich Steinkopff Verlag GmbH and Co. KG  

Background: D-dimer levels are used in several clinical settings, such as in predicting venous thrombosis, cardioembolic stroke and cancer status. In the present study, we investigated the associations between plasma D-dimer levels at admission, clinical characteristics and mortality at discharge in cryptogenic stroke patients. We also investigated whether D-dimer levels can predict long-term outcomes in those patients, including those with and without right-to-left shunt (RLS). Methods: Acute cryptogenic stroke patients (n = 295, 72 ± 13 years old) were consecutively enrolled and retrospectively analyzed. We defined the cryptogenic stroke as an undetermined etiology according to the Trial of Org 10172 in Acute Stroke Treatment criteria. Plasma D-dimer levels at admission were evaluated. Assessments for RLS were performed using saline contrast-transcranial Doppler ultrasonography or contrast-transesophageal echography. Survivors (at discharge) underwent follow-up for up to 3 years after stroke onset. Results: Of the total enrolled cohort, 17 patients died at discharge. D-dimer levels correlated with initial National Institutes of Health Stroke Scale (NIHSS) score (r = 0.391, P OpenSPiltSPi 0.001) and were associated with mortality at discharge [odds ratio 1.04
95% confidence interval (CI) 1.00–1.08, P = 0.049] after adjusting for age, sex and initial NIHSS score. Of the 278 survivors at discharge, 266 patients were evaluated to assess RLS during hospitalization, and 62 patients (23.3%) exhibited RLS. According to the median plasma D-dimer levels at admission (0.7 µg/ml), the patients were divided into a low D-dimer group (n = 136, OpenSPiltSPi median) and a high D-dimer group (n = 130, ≥ median). Patients in the high D-dimer group were older, more frequently female, had a lower BMI, had a higher prevalence of cancer and had greater initial neurological severity compared to the patients in the low D-dimer group. During the follow-up period (median, 1093 days), 31 patients developed recurrent stroke and 33 patients died. High D-dimer levels at admission were independently associated with recurrent stroke and all-cause mortality [hazard ratio (HR) 3.76
95% CI 1.21–14.1, P = 0.021) in patients with RLS, but not in those without RLS (HR 1.35
95% CI 0.74–2.50, P = 0.335). Conclusions: Increased D-dimer levels at admission were associated with mortality at discharge in cryptogenic stroke patients. In addition, high D-dimer levels were also associated with long-term outcomes in cryptogenic stroke patients with RLS.

DOI： 10.1007/s00415-018-8742-x

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Dr. Dietrich Steinkopff Verlag GmbH and Co. KG  

Stroke-associated infection (SAI) is a common and serious complication of stroke. This study aimed to assess the effects of SAI on patient mortality and functional outcome at 3 months after stroke onset. We retrospectively analyzed 809 consecutive patients with acute stroke (517 men and 292 women
median age, 72 years) who were admitted to our department between September 2014 and June 2016. SAI was defined as an infection diagnosed during the hospitalization period. Poor outcome was defined as a modified Rankin Scale (mRS) score of 3–5 or death (mRS score of 6). The effect of SAI on functional outcome was evaluated using a multivariate logistic regression analysis. SAI occurred in 169 patients (20.9%)
of these, 106 (62.7%) had pneumonia, 23 (13.6%) had a urinary-tract infection, and 40 (23.7%) had other types of infection. Patients with SAI were older, more likely to be female, had lower body mass indices, had higher stroke severity, and were more likely to have atrial fibrillation and a history of ischemic heart disease than patients without SAI. Poor functional outcome and mortality were more common in patients with SAI than in patients without SAI (poor functional outcome 41.8 vs. 4.8%, mortality 24.3 vs. 3.9%, respectively). After adjusting for age, sex, stroke severity, and various comorbidities, SAI was independently associated with poor functional outcome [odds ratio (OR) 6.88
95% confidence interval (CI) 3.72–12.73] and mortality (OR 4.45, 95% CI 2.27–8.72) at 3 months after stroke onset. Our results suggest that SAI during the hospitalization period is independently associated with 3-month poor functional outcome and mortality.

DOI： 10.1007/s00415-017-8714-6

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：W.B. Saunders  

Background: Poststroke infection (PSI) is common and is usually associated with a severe prognosis. We investigated the association between PSI and thyroid hormones, which are critical to immune regulation, in patients with acute stroke. Methods: We retrospectively enrolled 520 consecutive patients with acute ischemic stroke (326 men
age, 71.9 ± 13.2 years) admitted to our department between September 2014 and June 2016. The impact of serum thyroid hormone levels measured at admission (thyroid-stimulating hormone [TSH], free triiodothyronine [FT3], and free thyroxine [FT4]) on the PSI was evaluated using multivariate logistic regression analysis. Results: We diagnosed 107 patients (20.6%
pneumonia, 65
urinary tract infection, 19
others, 23) with PSIs. While age (P &lt
.001), body mass index (P =.0012), preadmission modified Rankin scale score (P =.0001), National Institutes of Health Stroke Scale score on admission (P &lt
.001), admission FT3 level (P &lt
.001), atrial fibrillation (P &lt
.001), and ischemic heart disease (P =.0451) were significantly associated with PSI, we found no relationship among TSH levels, FT4 levels, and PSI occurrence. After multivariate adjustment, patients with PSIs were more frequently in the Q1 quartile (≤2.25 pg/mL) than in the Q2 (2.26-2.55 pg/mL
P =.0251), Q3 (2.56-2.89 pg/mL
P =.0007), or Q4 (≥2.90 pg/mL
P =.0010) quartiles of FT3 levels. Moreover, low FT3 levels (&lt
2.29 pg/mL) were independently associated with PSI occurrence (P =.0013). Conclusions: Low FT3 levels at admission are independently associated with PSI occurrence.

DOI： 10.1016/j.jstrokecerebrovasdis.2017.09.012

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記述言語：英語  

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DOI： 10.1016/j.jns.2016.06.063

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：S. Karger AG  

BACKGROUND: We aimed to clarify associations between pre-admission risk scores (CHADS2, CHA2DS2-VASc, and HAS-BLED) and 2-year clinical outcomes in ischemic stroke or transient ischemic attack (TIA) patients with non-valvular atrial fibrillation (NVAF) using a prospective, multicenter, observational registry. METHODS: From 18 Japanese stroke centers, ischemic stroke or TIA patients with NVAF hospitalized within 7 days after onset were enrolled. Outcome measures were defined as death/disability (modified Rankin Scale score ≥3) at 2 years, 2-year mortality, and ischemic or hemorrhagic events within 2 years. RESULTS: A total of 1,192 patients with NVAF (527 women; mean age, 78 ± 10 years), including 1,141 ischemic stroke and 51 TIA, were analyzed. Rates of death/disability, mortality, and ischemic or hemorrhagic events increased significantly with increasing pre-admission CHADS2 (p for trend <0.001 for death/disability and mortality, p for trend = 0.024 for events), CHA2DS2-VASc (p for trend <0.001 for all), and HAS-BLED (p for trend = 0.004 for death/disability, p for trend <0.001 for mortality, p for trend = 0.024 for events) scores. Pre-admission CHADS2 (OR per 1 point, 1.52; 95% CI 1.35-1.71; p <0.001 for death/disability; hazard ratio (HR) per 1 point, 1.23; 95% CI 1.12-1.35; p <0.001 for mortality; HR per 1 point, 1.14; 95% CI 1.02-1.26; p = 0.016 for events), CHA2DS2-VASc (1.55, 1.41-1.72, p < 0.001; 1.21, 1.12-1.30, p < 0.001; 1.17, 1.07-1.27, p < 0.001; respectively), and HAS-BLED (1.33, 1.17-1.52, p < 0.001; 1.23, 1.10-1.38, p < 0.001; 1.18, 1.05-1.34, p = 0.008; respectively) scores were independently associated with all outcome measures. CONCLUSIONS: In ischemic stroke or TIA patients with NVAF, all pre-admission risk scores were independently associated with death/disability at 2 years and 2-year mortality, as well as ischemic or hemorrhagic events within 2 years.

DOI： 10.1159/000487896

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Medical Association of Nippon Medical School  

Background and Purpose: It is clinically important to evaluate time course changes in symptomatic middle cerebral artery (MCA) stenotic plaques because of likely recurrence. The objective of this study is to determine whether contrast-enhanced high-resolution magnetic resonance imaging (MRI) is a feasible method for this purpose. Methods: Contrast-enhanced, high-resolution, 3D turbo spin-echo images with low refocusing flip angle control (3D LOWRAT) applied to 7 patients with symptomatic MCA stenosis were evaluated at the initial (1 month after stroke onset) and follow-up (7 months after stroke onset) stages, and statistical variables, including plaque-to-thalamus signal intensity ratio, degree of stenosis, and stroke recurrence obtained at the 2 stages, were compared. Stenotic change at the initial stage was compared to that at the follow-up stage using MR angiography. Results: In 4 of the 7 patients, the signal intensity ratio measured at the follow-up stage was lower than that measured at the initial stage and in 1 patient, the stenosis subsequently improved. We used a Chi-Square Test. In the other 3 patients, the signal intensity ratios did not differ between the 2 stages, and ischemic stroke occurred in 2 of these 3 patients. Conclusion: Gadolinium contrast enhancement was found to be useful for effective evaluation of time course changes in the stability of symptomatic MCA stenotic plaques.

DOI： 10.1272/jnms.2018_85-4

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Japanese Circulation Society  

Background: Insufficient anticoagulant intensity on admission is common in stroke patients with atrial fibrillation (AF) on vitamin K antagonist (VKA) therapy. Nevertheless, the effects of VKA under-treatment on stroke severity or arterial occlusion are not well known. The aim of the present study was to investigate the relationship between insufficient VKA therapy and stroke severity, or the site of arterial occlusion in patients with acute ischemic stroke (AIS) and AF. Methods and Results: From March 2011 through July 2016, 446 consecutive patients with AF and AIS were recruited. Of the 446 patients, 364 (167 women
median age, 79 years
IQR, 71–86 years) with anterior-circulation stroke were assessed to investigate the effects of insufficient VKA. Of these, 281 were on no anticoagulant, 53 were undertreated with a VKA, and 30 were sufficiently treated with VKA on admission (PT-INR ≥2.0 for patients &lt
70 years and PT-INR ≥1.6 for ≥70 years old). On multivariate analysis, insufficient VKA was independently associated with severe stroke (i.e., initial NIHSS score ≥10
OR, 2.70, P=0.022) and higher prevalence of proximal artery occlusion (OR, 1.91
P=0.039) compared with no anticoagulant therapy. Conclusions: Insufficient VKA therapy on admission was associated with higher severity of stroke and higher prevalence of proximal artery occlusion in patients with AF and acute anterior-circulation stroke compared with no anticoagulant medication.

DOI： 10.1253/circj.CJ-17-1110

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DOI： 10.1159/000490461

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：SPRINGER HEIDELBERG  

Cortical superficial siderosis (cSS) is a pathologic and radiologic diagnosis of hemosiderin deposition in subpial brain layers. However, cSS has not been fully studied in patients with acute stroke. Here, we investigated the prevalence of cSS in patients with acute stroke and analyzed the relationship between cSS and different clinical and neuroimaging characteristics. From September 2014 through June 2016, consecutive patients with acute stroke who were admitted to our department were retrospectively investigated. We analyzed the prevalence of cSS and the associations between cSS and risk factors, the topographic distribution of cerebral microbleeds (CMBs), and the severity of white matter lesions (WMLs). In total, 739 patients (589 patients with ischemic stroke/transient ischemic stroke [IS/TIA] and 150 with intracerebral hemorrhage [ICH]; mean age, 71.4 years) were enrolled. We identified cSS in six (1.0%) patients with IS/TIA and seven (4.7%) patients with ICH. The presence of cSS was associated with ICH (P &lt; 0.0001), WMLs (P = 0.0105), and lobar and non-lobar CMBs (both P &lt; 0.0001); no associations between cSS and age, sex, cardiovascular risk factors, IS subtype classification, or antiplatelet and anticoagulant therapy were found. In a multivariable logistic regression analysis, high numbers of lobar CMBs (ae&lt;yen&gt; 2; odds ratio, 11.03; 95% confidence interval, 2.03-205.40; P = 0.0029) were independently associated with cSS. Furthermore, cSS was often located near lobar CMBs. Our results suggest that cSS is prevalent in ICH and is independently associated with lobar CMBs; however, no associations between cSS and other risk factors or comorbidities were observed.

DOI： 10.1007/s00415-017-8646-1

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Given the abundance of stroke patients and deaths from stroke worldwide, many studies concerning the aftermath of stroke are being carried out. To reveal the precise effect of ischemic infarction, we conducted a comprehensive gene expression analysis. Alongside a middle cerebral artery occlusion (MCAO) Sprague-Dawley rat model, we used a group undergoing sham surgery for comparison, which was the same as MCAO surgery but without blood vessel occlusion. Subsequently, infarction of the brains of MCAO-treated rats occurred, but did not occur in the sham-treated rats. Using whole blood, we carried out DNA microarray analysis, revealing the gene expression alterations caused by stroke. Downregulation of immune pathways and cluster of differentiation (CD) molecules indicated immunodepression. By conducting miRNA microarray analysis, we extracted seven miRNAs as significantly regulated: miR-107-5p, miR-383-5p, miR-24-1-5p, mir-191b, miR-196b-5p, and miR-3552 were upregulated, and mir-194-1 was downregulated. Among these seven miRNAs, three had one target mRNA each that was extracted as differentially expressed, and the expression levels of all pairs were inversely correlated. This indicates the occurrence of miRNA-mRNA regulatory systems in blood: between miR-107-5p and H2A histone family member Z (H2afz), miR-196b-5p and protein tyrosine phosphatase receptor type C (Ptprc), and miR-3552 and serine/arginine-rich splicing factor 2 (Srsf2). Moreover, six miRNAs had matching human miRNAs with similar sequences, which are potential human stroke biomarkers.

DOI： 10.3390/ijms18112335

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記述言語：日本語   出版者・発行元：(NPO)日本脳神経血管内治療学会  

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記述言語：日本語   出版者・発行元：(NPO)日本脳神経血管内治療学会  

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記述言語：日本語   出版者・発行元：(NPO)日本脳神経血管内治療学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：ELSEVIER SCIENCE BV  

Background and Purpose: Recent studies using magnetic resonance imaging (MRI) have reported that wake-up stroke (WUS) patients may be able to be treated using tissue-plasminogen activator (tPA) when showing no ischemia on fluid-attenuated inversion recovery (Negative-FLAIR). We investigated the frequency of WUS and calculated what percentage of WUS patients with Negative-FLAIR meets most of the conventional tPA criteria. We did not include a time parameter in this study.
Methods: Consecutive patients with acute stroke affecting the anterior circulation who presented within 12 h of onset were enrolled. All patients were examined using diffusion-weighted imaging (DWI) and FLAIR. As large infarctions are excluded from tPA therapy, an Alberta Stroke Program Early Computed Tomography Score (DWI ASPECTS) of 3 was used as the upper limit for exclusion.
Results: A total of 816 consecutive patients were included in the study and were separated into two groups; 163 (20%) WUS patients as the WUS group, and 653 (80%) non-WUS patients as the non-WUS group. The median National Institutes of Health Stroke Scale (NIHSS) score on admission was 7 (interquartile range, 3-17) in the WUS group and 8 (3-16) in the non-WUS group (p = 0.313). MRI study revealed Negative-FLAIR in 67 (41%) of 163 patients in the WUS group. Of the 67 patients with Negative-FLAIR, 19 patients were excluded from tPA therapy. Therefore, 48 (29%) of the 163 wake-up stroke patients met the tPA criteria.
Conclusions: About 30% of WUS patients may be candidates for tPA therapy based upon Negative-FLAIR findings.

DOI： 10.1016/j.jns.2017.09.042

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：WILEY  

Background and purposeAnticoagulant treatment with a vitamin K antagonist (VKA) has been reported to reduce stroke severity when patients with atrial fibrillation (AF) suffer acute ischaemic stroke (AIS). Direct oral anticoagulant (DOAC) therapy also has the potential to reduce the initial severity of AIS. However, the effect of DOAC therapy on the severity of AIS is not well known. The aim of the present study was to investigate the effect of DOACs on initial stroke severity in patients with AIS and non-valvular AF.
MethodsFrom March 2011 to July 2016, consecutive patients with AIS having non-valvular AF were recruited. The effects of prior DOAC treatment on severity were assessed by multivariate logistic regression analyses.
ResultsA total of 484 patients [208 women; median age 79 (interquartile range, 71-85) years; National Institutes of Health Stroke Scale (NIHSS) score 9 (interquartile range, 3-20)] were enrolled. Of these, 352 (73%) were on no anticoagulant medication, 54 (11%) were undertreated with a VKA, 35 (7%) were sufficiently treated (admission prothrombin time-international normalized ratio: 2.0 for patients &lt;70 years old and 1.6 for 70 years old) with a VKA and 43 (9%) were on a DOAC. The initial NIHSS score (median 10 in patients with no anticoagulation, 13 in undertreated VKA, 7 in sufficient VKA and 6 in DOAC, P = 0.018) was different among the groups. Multivariate analysis showed that DOAC was independently and negatively associated with severe (initial NIHSS score 10) stroke (odds ratio, 0.39; P = 0.041), compared with no anticoagulant therapy.
ConclusionsDirect oral anticoagulant treatment prior to the event should reduce initial stroke severity in patients with AIS and non-valvular AF.

DOI： 10.1111/ene.13405

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記述言語：日本語   出版者・発行元：(NPO)日本脳神経血管内治療学会  

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記述言語：日本語   出版者・発行元：(一社)日本神経学会  

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記述言語：英語   出版者・発行元：Elsevier BV  

DOI： 10.1016/j.omtm.2017.06.005

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：ELSEVIER SCIENCE BV  

Background: The safety of intravenous thrombolysis (IVT) and endovascular therapy (EVT) in patients treated with DOAC is unclear. We investigated whether recanalization therapy in patients treated with DOAC is safe.
Methods: A nationwide, multicenter, retrospective cohort questionnaire survey was conducted to investigate the: (1) frequency of intracerebral hemorrhage (ICH) after recanalization therapy in patients treated with DOAC; (2) independent factors related to ICH; (3) relationship between last intake time of DOAC and ICH; and (4) comparison of ICH frequency between patients treated with DOAC, vitamin K antagonist (VKA), and no-anticoagulation (no-ACT) (control).
Results: One hundred eighteen stroke centers returned the questionnaire and 100 patients (56 IVT alone, 29 EVT alone, and 15 both IVT and EVT) on DOAC were registered. The frequency of asymptomatic and symptomatic (&gt;=. 4-point NIHSS score increase) ICH within 24 h in DOAC patients were 18% and 2%, and were not different compared with the VKA and no-ACT groups (p = 0.728; and p = 0.626). On multivariate analysis, systolic blood pressure (OR, 1.04; p&lt;0.001) and blood glucose (OR, 1.02; p = 0.019) were independent factors for ICH. Among the 52 patients with a known last intake time of DOAC, the rate of ICH was higher in patients 54 h from last intake than those &gt;4 h (38% vs. 10%, p = 0.033).
Conclusions: Risk of ICH after reperfusion therapy in patients treated with DOAC should be low. Systolic blood pressure, glucose level, and DOAC intake time appear to be factors for ICH. (C) 2017 Elsevier B.V. All rights reserved.

DOI： 10.1016/j.jns.2017.06.004

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：WILEY  

Aim: Albuminuria and a low estimated glomerular filtration rate (eGFR) are widely recognized indices of kidney dysfunction and have been linked to cardiovascular events, including stroke. We evaluated albuminuria, measured using the urinary albumin/creatinine ratio (UACR), and the eGFR in the acute phase of ischaemic stroke, and investigated the clinical characteristics of ischaemic stroke patients with and those without kidney dysfunction.
Methods: The study included 422 consecutive patients admitted between June 2010 and May 2012. General blood and urine examinations were performed at admission. Kidney dysfunction was defined as a low eGFR (&lt; 60mL/min per 1.73m(2)), high albuminuria (30mg/g creatinine), or both. Neurological severity was evaluated using the National Institutes of Health Stroke Scale (NIHSS) at admission and the modified Rankin scale (mRS) at discharge. A poor outcome was defined as a mRS score of 3-5 or death. The impacts of the eGFR and UACR on outcomes at discharge were evaluated using multiple logistic regression analysis.
Results: Kidney dysfunction was diagnosed in 278 of the 422 patients (65.9%). The eGFR was significantly lower and UACR was significantly higher in patients with a poor outcome than in those with a good outcome. In multivariate analyses performed after adjusting for confounding factors, UACR &gt; 31.2mg/g creatinine (OR, 2.58; 95% CI, 1.52-4.43; P=0.0005) was independently associated with a poor outcome, while a low eGFR was not associated.
Conclusions: A high UACR at admission may predict a poor outcome at discharge in patients with acute ischaemic stroke.

DOI： 10.1111/nep.12745

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：LIPPINCOTT WILLIAMS & WILKINS  

BACKGROUND AND PURPOSE: We investigated whether administration of edaravone, a free radical scavenger, before or during tissue-type plasminogen activator (tPA) can enhance early recanalization in a major arterial occlusion. METHODS: The YAMATO study (Tissue-Type Plasminogen Activator and Edaravone Combination Therapy) is an investigator-initiated, multicenter (17 hospitals in Japan), prospective, randomized, and open-label study. Patients with stroke secondary to occlusion of the M1 or M2 portion of the middle cerebral artery and within 4.5 hours of the onset were studied. The subjects were randomly allocated to the early group (intravenous edaravone [30 mg] was started before or during tPA) and the late group (edaravone was started after tPA and the assessment of early recanalization). RESULTS: One-hundred sixty-five patients (96 men; median age [interquartile range], of 78 [69-85] years) were randomized 1:1 to either the early group (82 patients) or the late group (83 patients). Primary outcome, defined as an early recanalization 1.5 hour after tPA, was observed in 53% of the early group and in 53% of the late group (P=1.000). About secondary outcomes, the rate of significant recanalization of ≥50% was not different between the 2 groups (28% versus 34%; P=0.393). The symptomatic intracerebral hemorrhage has occurred in 4 patients (5%) in the early group and in 2 patients (2%) in the late group (P=0.443). The favorable outcome (modified Rankin Scale score of 0-2) at 3 months was also similar between the groups (53% versus 57%; P=0.738). CONCLUSIONS: The timing of edaravone infusion does not affect the rate of early recanalization, symptomatic intracerebral hemorrhage, or favorable outcome after tPA therapy. CLINICAL TRIAL REGISTRATION: URL: http://www.umin.ac.jp/ctr/index-j.htm. Unique identifier: UMIN000006330.

DOI： 10.1161/STROKEAHA.116.015042

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：ELSEVIER SCIENCE BV  

Background: The presence of white matter lesions (WML) is an indicator of small vessel disease; however, the underlying pathological mechanisms are still unclear. We aimed to investigate the association of estimated glomerular filtration rate (eGFR) and urinary albumin-to-creatinine ratio (UACR) with WML severity in first-ever stroke patients.
Methods: We retrospectively enrolled 284 consecutive patients (177 male; median age 72 years) admitted to our stroke center between May 2010 and January 2012. eGFR and UACR measurements were performed on admission. WML severity was assessed using the Fazekas classification. Severe WML was defined as a Fazekas grade of 2 or higher. The impact of eGFR and UACR on severe WML was evaluated using multiple logistic regression analysis.
Results: Age (P &lt; 0.0001), sex (P = 0.0094), eGFR (P = 0.0173), UACR (P = 0.0001), hypertension (P = 0.0436), and brain natriuretic peptide (P = 0.0354) were significantly associated with severe WML. On multivariable logistic regression analysis, high UACR (&gt;= 39.6 mg/g creatinine, P = 0.039), but not low eGFR (&lt;= 74 ml/min/1.73 m(2), P = 0.3672), was independently associated with severe WML. Comparisons between the UACR levels showed that severe WML was more frequent in the UACR mg/g creatinine group than in the UACR &lt;30.0 mg/g creatinine group after multivariate adjustment (OR, 225; 95% CI, 1.04-5.00; P = 0.039). However, there was no significant association between eGFR and severe WML.
Conclusions: Our data suggest that high UACR, but not eGFR, is independently associated with severe WML. (C) 2017 Elsevier B.V. All rights reserved.

DOI： 10.1016/j.jns.2017.01.011

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：ELSEVIER SCIENCE BV  

Background: Reduced glomerular filtration rate (GFR) and albuminuria have been independently associated with an increased risk of stroke and unfavorable long-term outcomes. However, the association between GFR, albuminuria, and early neurological deterioration (END) in patients with ischemic stroke has not been well studied to date. We therefore investigated the ability of estimated GFR (eGFR) and albuminuria to predict END in patients with acute ischemic stroke.
Methods: We retrospectively enrolled 294 patients that were admitted to our stroke center with acute ischemic stroke between January 2011 and September 2012. General blood and urine examinations, including eGFR and urinary albumin/creatinine ratio (UACR) measurements, were performed on admission. Kidney dysfunction was defined by a low eGFR value (&lt;60 mL/min/1.73 m(2)) and/or increased albuminuria (&gt;= 30 mg/g creatinine). END was defined as a &gt;= 2-point increase in the National Institutes of Health Stroke Scale (NIHSS) score within 7 days after admission.
Results: Kidney dysfunction was diagnosed in 200 of the 294 patients (68.0%). END was observed in 60 patients (20.4%). Age, blood glucose level on admission, UACR on admission, and NIHSS score on admission were significantly associated with END, while no relationship between eGFR on admission and END was identified. A multivariable logistic regression analysis showed that END was positively associated with high UACR (&gt;= 39.6 mg/g creatinine) and a high NIHSS score (6 points).
Conclusions: Our data suggest that high UACR on admission may predict END in patients with acute ischemic stroke. Larger prospective studies are required to validate the correlation between albuminuria and END. (C) 2016 Elsevier B.V. All rights reserved.

DOI： 10.1016/j.jns.2016.11.007

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記述言語：日本語   出版者・発行元：日本神経学会  

<p>症例は66歳男性．頭痛・眼痛に続き，複視も出現し入院．左眼に外転麻痺，眼球突出を認め，Tolosa-Hunt症候群を疑いメチルプレドニゾロン1 g×3日で加療したが改善無し．造影MRI，髄液，IgG4，ANCAなどは異常を認めず，HbA1c 9.2と糖尿病を認めた．発症1週後から，鼻背に帯状疱疹が出現し角膜病変を伴った．眼部帯状疱疹と診断し，アシクロビル15 mg/kgを開始，プレドニゾロン1 mg/kgから漸減した．眼痛・皮疹は速やかに改善，眼球運動は数ヶ月で徐々に改善した．眼部帯状疱疹で複視が皮疹に先行することは稀である．未治療糖尿病と強力なステロイド治療が，皮疹の出現を抑制していた可能性を推測した．</p>

DOI： 10.5692/clinicalneurol.cn-000972

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記述言語：日本語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Societas Neurologica Japonica  

A 67-year-old woman developed weakness of the entire left side of the body and disturbance of consciousness, and was admitted to our hospital. She had atrial fibrillation (AF) on arrival at the hospital. Diffusion weighted magnetic resonance imaging showed high intensity area in the right basal ganglia, and magnetic resonance angiography showed occlusion of the right internal carotid artery (ICA). Thrombolytic therapy with intravenous tissue plasminogen activator (IV tPA) was administered 225 minutes after onset, and endovascular procedure also performed. After endovascular therapy, the patient had successful recanalization of the right ICA. Transesophageal echocardiography (TEE) showed a mass in the left atrium. Cardiac surgery for the excision of a left atrial mass and the maze procedure for atrial fibrillation were performed on the 29th hospital day. The mass was pathologically confirmed as thrombus. Follow up TEE after cardiac surgery revealed recurrence of thrombus at the both origin of pulmonary vein in the left atrium. Finally, the thrombus was disappeared at 6-month after onset with taking warfarin. She had no stroke events during the clinical course.

DOI： 10.5692/clinicalneurol.cn-001069

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：KARGER  

Background: Thrombus visualization in patients with acute ischemic stroke has been detected and reported using various imaging modalities. T1-weighted imaging (T1-WI) can depict thrombi as hyperintense signals within vessels. Moreover, in addition to thrombi, T1-WI hyperintensities in arteries may suggest arterial dissection. However, the frequency of and factors related to the T1-hyperintense vessel sign (T1-HVS) are not fully known. The aim of this study was to clarify the prevalence of and related factors for the T1-HVS in patients with acute ischemic stroke.
Methods: From September 2014 through December 2015, consecutive acute ischemic stroke patients who were admitted to our stroke unit within 7 days from symptom onset were retrospectively recruited from the prospective registry. A T1-HVS was defined as the presence of a hyperintense signal, with intensity higher than surrounding brain, within the vessel lumen. Moreover, T1-HVSs were separated into filled T1-HVSs (hyperintensity fills whole vessel lumen) and non-filled T1-HVSs. The frequency of the T1-HVS and the timing of emersion and the relationship between the presence of the T1-HVS and arterial occlusion were assessed. Results: A total of 399 patients (139 women; median age 73 years; National Institutes of Health Stroke Scale score 3) were enrolled in the present study. Of these, 327 (82%) patients had T1-WI on admission. Two hundred and sixty-seven (67%) subjects had at least one follow-up T1-WI (median 6 days after admission), and 134 (34%) cases had &gt;= 2 follow-up T1-WI examinations. The T1-HVS was observed in 18 patients during admission; therefore, the frequency of the T1-HVS in acute ischemic stroke patients was 4.5% (95% CI 2.5-6.5%). All but one (94%) of the T1-HVSs were first observed on follow-up imaging, and the median number of days from onset to T1-HVS appearance was 9. For patients having initial major artery occlusion and follow-up MRI (n = 95), sensitivity and specificity of the T1-HVS for persistent arterial occlusion on follow-up MR angiography were 22 and 100%, respectively. T1-HVS persisted for a few months and then normalized. Although there were no significant differences between filled and non-filled T1-HVS, more patients with non-filled T1-HVS had arterial dissection (43%) than those with filled T1-HVS (9%, p = 0.245). Conclusion: The T1-HVS was observed in 4.5% of acute ischemic stroke patients. T1-HVSs appeared in the subacute phase in arteries with persistent occlusion and remained for a few months. (C) 2017 S. Karger AG, Basel.

DOI： 10.1159/000479593

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記述言語：英語   出版者・発行元：一般社団法人 日本内科学会  

<p>Ataxic hemiparesis (AH) is a classic lacunar syndrome associated with localized damage to the pons, internal capsule, thalamus, or corona radiata. A depression of metabolic activity known as crossed cerebellar diaschisis (CCD) is frequently observed in the cerebellar hemisphere contralateral to the site of the lesion in patients with AH. Though small cortical or subcortical lesions may result in AH, such occurrences are rare. The current report details the case of a patient with AH resulting from acute infarction associated with localized lesions of the postcentral gyrus who presented without CCD. </p>

DOI： 10.2169/internalmedicine.8806-17

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：ELSEVIER SCIENCE BV  

Objective: This study was performed to investigate whether the Penumbra 5MAX ACE is superior to other Penumbra systems. Materials and Methods: We performed a retrospective, single center analysis of patients with acute ischemic stroke with occlusion of the internal carotid artery or middle cerebral artery (M1 segment) who underwent endovascular therapy using a Penumbra system. The reperfusion success rate, puncture-to-revascularization time, and number of passes were assessed. Multivariate regression analysis was conducted to evaluate independent factors related to revascularization within 60 minutes. Successful revascularization was defined by a thrombolysis in cerebral infarction score &gt;= 2b. Results: The Penumbra 5MAX ACE was used in 24 of the 40 patients (60%). Although the revascularization success rate was similar between patient groups (P = .229), the number of passes was significantly lower (1.5 +/- .8 versus 2.6 +/- 1.3, P = .006) and the puncture-to-revascularization time was shorter (50 +/- 26 minutes versus 116 +/- 69 minutes, P = .002) in patients treated with the Penumbra 5MAX ACE. The Penumbra 5MAX ACE was identified as an independent factor for early revascularization (odds ratio, 5.80; P = .041). Among patients with a premorbid modified Rankin Scale score of 0-1, a modified Rankin Scale score of 0-2 at 3 months was observed in 15 of the 19 patients (79%) treated with the Penumbra 5MAX ACE and in 8 of the 16 (50%) who were not (P = .072). Conclusion: Acute revascularization therapy using the Penumbra 5MAX ACE can achieve rapid successful recanalization and tend to improve clinical outcomes.

DOI： 10.1016/j.jstrokecerebrovasdis.2016.08.016

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：SPRINGER  

The safety and efficacy of non-vitamin K oral anticoagulant (NOAC) compared with warfarin in treating patients with non-valvular atrial fibrillation (NVAF) who developed acute ischemic stroke or transient ischemic attack (AIS/TIA), particularly those receiving tissue-plasminogen activator (tPA) therapy, remains unclear. Between April 2012 and December 2014, we conducted a multicenter prospective cohort study to assess the current clinical practice for treating such patients. We divided the patients into two groups according to the administration of oral anticoagulants (warfarin or NOACs) and tPA therapy. The risk of any hemorrhagic or ischemic event was compared within 1 month after the onset of stroke. We analyzed 235 patients with AIS/TIA including 73 who received tPA therapy. Oral anticoagulants were initiated within 2-4 inpatient days. NOACs were administered to 49.8 % of patients, who were predominantly male, younger, had small infarcts, lower NIHSS scores, and had a lower all-cause mortality rate (0 vs. 4.2 %, P = 0.06) and a lower risk of any ischemic events (6.0 vs. 7.6 %, P = 0.797) compared with warfarin users. The prevalence of all hemorrhagic events was equivalent between the two groups. Early initiation of NOACs after tPA therapy appeared to lower the risk of hemorrhagic events, although there was no significant difference (0 vs. 5.6 %, P = 0.240). Although more clinicians are apt to prescribe NOACs in minor ischemic stroke, NOAC treatment may provide a potential benefit in such cases. Early initiation of NOACs after tPA therapy may reduce the risk of hemorrhagic events compared with warfarin.

DOI： 10.1007/s11239-016-1376-x

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記述言語：日本語   出版者・発行元：(NPO)日本脳神経血管内治療学会  

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記述言語：日本語   出版者・発行元：(NPO)日本脳神経血管内治療学会  

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記述言語：日本語   出版者・発行元：(NPO)日本脳神経血管内治療学会  

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記述言語：日本語   出版者・発行元：(NPO)日本脳神経血管内治療学会  

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記述言語：日本語   出版者・発行元：(NPO)日本脳神経血管内治療学会  

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記述言語：日本語   出版者・発行元：(NPO)日本脳神経血管内治療学会  

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記述言語：日本語   出版者・発行元：(NPO)日本脳神経血管内治療学会  

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記述言語：日本語   出版者・発行元：(NPO)日本脳神経血管内治療学会  

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記述言語：日本語   掲載種別：研究論文（学術雑誌）  

A 64-year-old man with fever, appetite loss, and pain in the back of the neck visited our hospital. We diagnosed him as having bacterial meningitis because of pleocytosis of the cerebrospinal fluid, and started treatment with antibiotics. Multiple cerebral infarcts were found on brain MRI. We suspected that the origin of the bacterial meningitis was infective endocarditis, and administered Cefepime and Gentamicin according to the guidelines for treatment of infective endocarditis. Three days later, he became drowsy and had myoclonus and flapping of the extremities. An electroencephalograph showed generalized periodic discharge and a triphasic wave pattern. We thought that the cause of disturbance in consciousness was Cefepime-induced encephalopathy, and stopped administration of Cefepime. A few days later, he became clear, and the myoclonus and flapping disappeared. It was difficult to distinguish between non-convulsive status epilepticus and Cefepime-induced encephalopathy. However, since stopping Cefepime treatment had made the patient clear, we diagnosed his condition as Cefepime-induced encephalopathy, which often occurs in patients with renal or liver dysfunction, or in brain infarction or meningitis, which results in blood-brain barrier disruption. Thus, care should be taken when administering Cefepime to such patients.

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記述言語：英語   出版者・発行元：ELSEVIER SCIENCE BV  

DOI： 10.1016/j.jns.2016.07.050

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：ELSEVIER SCIENCE BV  

A 59-year-old woman was admitted to our hospital because of repeated episodes of bilateral hand weakness. She had a 10-year history of combined estrogenprogestin therapy for menopausal symptoms. Magnetic resonance imaging on admission showed multiple hyperintense lesions in bilateral cerebral and cerebellar cortices on diffusion-weighted imaging. Transesophageal echocardiography showed thrombus formation on the aortic valve and moderate aortic insufficiency. Laboratory test demonstrated elevated CA125 (334.8 U/mL) and D-dimer (7.0 mu g/mL) levels. Trousseau's syndrome (cancer-related hypercoagulation) was considered, but various examinations showed only uterine adenomyosis and no evidence of cancer. Multiple cerebral infarctions were considered to be caused by Trousseau's syndromelike condition associated with uterine adenomyosis. CA125 and coagulation markers should be measured in adenomyosis patients treated with hormone replacement therapy, because a mucinous tumor and coagulation markers may be good markers for the risk of thromboembolism in such patients.

DOI： 10.1016/j.jstrokecerebrovasdis.2016.07.024

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Feasibility of performing MRI first for suspected hyperacute stroke patients in real-world practice has not been fully examined. Moreover, most past studies of reducing door-to-needle time (DNT) in intravenous thrombolysis were conducted using CT. The aim of this study was to evaluate the feasibility of an MRI-first policy and examine the effects of a quality improvement (QI) process for reducing DNT using MRI. METHODS: From January 2014 to August 2015, consecutive acute stroke patients who were treated with thrombolysis were prospectively enrolled into the present study. In principle, multimodal 1.5T-MRI was performed first for patients with suspected acute stroke. A step-by-step QI process for decreasing DNT, including prenotification by the emergency medical service, limiting the MRI sequence, and introduction of a rapid examination tool, was also implemented during this period. Time metrics for thrombolysis were compared between specific time periods. RESULTS: A total of 73 patients (27 women; median age 74years) were included in the present study. More than 80% of the patients were screened with MRI. More patients were managed with the MRI-first policy in the late phase (p=0.018). DNT (83min in the early phase, 68min in the middle phase, and 54min in the late phase, p<0.001) was significantly reduced across phases. The percentage of patients with DNT<60min increased significantly across time periods (p<0.001). CONCLUSION: An MRI-first policy was feasible, and DNT was substantially reduced with a QI process. This process may be applicable to other hospitals.

DOI： 10.1016/j.jns.2016.07.011

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：ELSEVIER SCIENCE BV  

Objective: Isolated deep subcortical infarcts develop as a result of occlusion of the penetrating arteries from the internal carotid artery (ICA) and the proximal (M1) and distal middle cerebral artery (MCA). However, the clinical and neuroimaging characteristics of infarcts due to the occlusion of the distal MCA penetrating artery are unclear.
Methods: Consecutive patients with ischemic stroke or transient ischemic attack with magnetic resonance imaging (MRI) performed within 2 days of onset were studied retrospectively. Using coronal MRI data, isolated deep subcortical infarcts were classified into two groups: 1) proximal group, described as being longer than they are wide, which were expected to be related to the occlusion of the ICA or M1 penetrating artery; and 2) distal group, described as oblong, which were expected to be associated with the occlusion of penetrating arteries from the distal MCA (M2/M3/M4).
Results: A total of 653 consecutive acute ischemic stroke patients (proximal group, 50 [7.7%]; distal group, 14 [2.1%]) were enrolled. Baseline clinical characteristics were not different between the 2 groups. Modified Rankin Scale scores were lower in the distal group than in the proximal group 3 months after stroke onset (1.43 +/- 0.36 vs. 226 +/- 1.35, p = 0.023). We measured the lengths of the infarcts in the X and Y directions using axial MRI. The X/Y ratio was larger in tile distal group than in the proximal group (1.3 +/- 0.6 vs. 0.7 +/- 02, p &lt; 0.01), which indicated that distal MCA penetrating artery infarcts appear more oblong on axial MRI.
Conclusions: One cause for deep subcortical infarction is the occlusion of the distal MCA penetrating arteries, which occurs in 22% of patients with deep subcortical infarctions. These patients had better clinical outcomes than those with ICA and M1 penetrating artery infarctions. Distal MCA penetrating artery infarctions appear oblong on axial MRI. (C) 2016 Elsevier B.V. All rights reserved.

DOI： 10.1016/j.jns.2016.07.005

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：ELSEVIER SCIENCE BV  

Background and purpose: The aim of this study was to investigate the association of admission serum thyroid hormone concentration with clinical characteristics and functional outcomes in patients after acute ischemic stroke.
Methods: We retrospectively enrolled 398 consecutive patients admitted to our stroke center between July 2010 and April 2012. Serum thyroid stimulating hormone (TSH), free triiodothyronine (FT3), and free thyroxine (FT4) were evaluated upon admission. Neurological severity was evaluated using the National Institutes of Health Stroke Scale (NIHSS) upon admission and the modified Rankin Scale (mRS) upon discharge. Poor outcome was defined as a mRS score of 3-5 or death (mRS score 6). Separate analyses were conducted according to outcome and quartile serum FT3 concentration.
Results: In total, 164 patients (41.2%) demonstrated a poor outcome. Age, male gender, blood glucose level, arterial fibrillation, dyslipidemia, smoking, NIHSS score, cardioembolic stroke type, and periventricular hyperintensities, but not FT4 or TSH, were significantly associated with poor functional outcome. Furthermore, poor functional outcome was independently associated with low FT3 (&lt;2.29 pg/mL). In comparisons between FT3 quartiles (Q1 [&lt;= 2.11 pg/mL], Q2 [2.12-2.45 pg/mL], Q3 [2.46-2.77 pg/mL], Q4 [&gt;= 2.78 pg/mL]), patients with poor outcomes were more frequent in Q1 than in Q4 after multivariate adjustment. Death was more frequent in Q1 than in Q4 after adjustment for risk factors and comorbidities, but this difference was non-significant after additional adjustment for age and NIHSS score.
Conclusions: Our data suggest that a lower FT3 value upon admission may predict a poor functional outcome in patients with acute ischemic stroke. Further large-scale prospective studies are required to clarify the role of thyroid hormone in the acute phase of ischemic stroke. (C) 2016 Elsevier B.V. All rights reserved.

DOI： 10.1016/j.jns.2016.06.063

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：ELSEVIER SCIENCE BV  

Spontaneous cervical artery dissection (sCAD) is a major cause of ischemic stroke in young adults. Frequently, sCAD involves multiple neck arteries, accounting for 13%-28% of the total sCAD cases. However, little is known about factors related to multiple sCAD. In this case, a 52-year-old man was admitted due to headache without aura. There was a personal history of migraine with aura and a family history of similar symptoms. The patient's younger brother had a left vertebral artery (VA) dissecting aneurysm and underwent endovascular occlusion of his parent artery at the age of 48. Magnetic resonance imaging of our admitted patient showed hyperintensities in the right internal carotid artery (ICA) without acute infarction, and magnetic resonance angiography revealed a narrowing of the right ICA. Angiography was then performed, which showed a trace of dissection of the left ICA and both VAs as well as the right ICA. The patient did not fulfill any major criteria of collagen vascular disease such as Ehlers-Danlos syndrome type IV or Loeys-Dietz syndrome. The data in our patient are quite similar to those reported in patients with single-nucleotide polymorphism (SNP) of PHACTR1. Obtaining the patient's informed consent, we analyzed a common SNP variation in the rs9349379[G] allele (PHACTR1), which has been reported to be associated with a lower risk of sCAD.

DOI： 10.1016/j.jstrokecerebrovasdis.2016.04.027

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記述言語：英語   出版者・発行元：ELSEVIER SCIENCE BV  

DOI： 10.1016/j.jns.2016.05.044

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：SAGE PUBLICATIONS LTD  

AIMS: This study was performed to determine the short-term risk-benefit profiles of patients treated with oral anticoagulation for acute ischemic stroke or transient ischemic attack using a multicenter, prospective registry. METHODS: A total of 1137 patients (645 men, 77 ± 10 years old) with acute ischemic stroke/transient ischemic attack taking warfarin (662 patients) or non-vitamin K antagonist oral anticoagulants (dabigatran in 205, rivaroxaban in 245, apixaban in 25 patients) for nonvalvular atrial fibrillation who completed a three-month follow-up survey were studied. Choice of anticoagulants was not randomized. Primary outcome measures were stroke/systemic embolism and major bleeding. RESULTS: Both warfarin and non-vitamin K antagonist oral anticoagulants were initiated within four days after stroke/transient ischemic attack onset in the majority of cases. Non-vitamin K antagonist oral anticoagulant users had lower ischemia- and bleeding-risk indices (CHADS2, CHA2DS2-VASc, HAS-BLED) and milder strokes than warfarin users. The three-month cumulative rate of stroke/systemic embolism was 3.06% (95% CI 1.96%-4.74%) in warfarin users and 2.84% (1.65%-4.83%) in non-vitamin K antagonist oral anticoagulant users (adjusted HR 0.96, 95% CI 0.44-2.04). The rate of major bleeding was 2.61% (1.60%-4.22%) and 1.11% (0.14%-1.08%), respectively (HR 0.63, 0.19-1.78); that for intracranial hemorrhage was marginally significantly lower in non-vitamin K antagonist oral anticoagulant users (HR 0.17, 0.01-1.15). Major bleeding did not occur in non-vitamin K antagonist oral anticoagulant users with a CHADS2 score <4 or those with a discharge modified Rankin Scale score ≤2. CONCLUSIONS: Stroke or systemic embolism during the initial three-month anticoagulation period after stroke/transient ischemic attack was not frequent as compared to previous findings regardless of warfarin or non-vitamin K antagonist oral anticoagulants were used. Intracranial hemorrhage was relatively uncommon in non-vitamin K antagonist oral anticoagulant users, although treatment assignment was not randomized. Early initiation of non-vitamin K antagonist oral anticoagulants during the acute stage of stroke/transient ischemic attack in real-world clinical settings seems safe in bleeding-susceptible Japanese population.

DOI： 10.1177/1747493016632239

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：WILEY-BLACKWELL  

BACKGROUND AND PURPOSE: The safety and feasibility of intravenous thrombolysis using recombinant tissue plasminogen activator (IV-tPA) were retrospectively compared between patients with unknown onset time and no ischemia on fluid-attenuated inversion recovery (negative FLAIR) and patients receiving standard therapy.
METHODS: Acute stroke patients with unknown onset times were treated using IV-tPA if they had: negative FLAIR; internal carotid artery and/or middle cerebral artery occlusion; and a diffusion-weighted imaging (DWI)-Alberta Stroke Programme Early CT Score &gt;= 5. All patients had abnormal DWI scans indicating an acute stroke. IV-tPA therapy was performed within 3-4.5 h of first found abnormal time (FAT). Patients who were admitted within 3-4.5 h of FAT and did not receive IV-tPA therapy despite the same imaging findings were extracted from our registry as controls.
RESULTS: There were 24 patients in the IV-tPA group and 28 in the control group. None of the IV-tPA group and 1 (4%) of the control group patients experienced symptomatic intracerebral hemorrhage (P = 1.000). The rate of dramatic recovery at day 7 (&gt;= 10-point reduction in the total National Institutes of Health Stroke Scale [NIHSS] score or NIHSS score of 0-1) was 46% in the IV-tPA group and 18% in the control group (P = .038). Multivariate regression analysis revealed that IV-tPA was an independent predictor of dramatic recovery at day 7 (odds ratio 13.74; 95% confidence interval, 1.95-96.92; P = .009).
CONCLUSIONS: IV-tPA may safely increase the rate of dramatic recovery in acute stroke patients with unknown onset times and negative FLAIR.

DOI： 10.1111/jon.12323

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記述言語：英語   出版者・発行元：NATURE PUBLISHING GROUP  

Alteplase is widely used for acute stroke at a dose of 0.6 mg/kg in Asian patients, whereas the standard in Europe and the USA is 0.9 mg/kg. The ENCHANTED study did not show that 0.6 mg/kg alteplase is noninferior to 0.9 mg/kg, as previously suggested, raising questions about standard practice in Asia.

DOI： 10.1038/nrneurol.2016.90

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記述言語：英語   出版者・発行元：ELSEVIER SCIENCE BV  

DOI： 10.1016/j.jns.2016.04.014

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記述言語：英語   出版者・発行元：WILEY-BLACKWELL  

DOI： 10.1111/ene.12977

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：ELSEVIER SCIENCE BV  

Background and purpose: Data on long-term outcomes after tissue-plasminogen activator (tPA) therapy are limited. We evaluated the rate of favorable outcomes and mortality at 5 years after tPA therapy and investigated factors related to long-term clinical outcomes.
Methods: Telephone interviews or interview letters were used to assess the modified Rankin Scale (mRS) scores at 3 months, 6 months, 1 year, 2 years, 3 years, 4 years, and 5 years after tPA therapy. Favorable outcome was defined as mRS 0-2. Multivariate logistic regression analysis was conducted to investigate factors associated with favorable outcomes and mortality at 5 years after tPA therapy.
Results: From 2005 to 2013, 256 (median age, 77 [interquartile range, 68-84] years; 157 [61%] males; median National Institutes of Health Stroke Scale score, 11 [5-18]) patients were enrolled. Kaplan-Meier curve showed that favorable outcomes after 5 years after tPA therapy occurred in 45% of the patients and that the mortality rate was 40%. Univariate analysis showed that onset-to-treatment time (OTT) was 121 (107-172) minutes in patients with favorable outcomes and 156 (126-171) minutes in patients with unfavorable outcomes (p = 0.016). In addition, OTT was 157 (133-172) minutes in the death group and 123 (106-169) minutes in the survival group (p = 0.001). Multivariate regression analysis indicated that OTT was an independent factor related to favorable outcomes (odds ratio 0.96, 95% confidence interval 0.93-0.99, p = 0.004) and mortality (odds ratio 1.04, 95% confidence interval 1.02-1.06, p = 0.001).
Conclusion: Early tPA administration can improve long-term clinical outcomes. (C) 2016 Elsevier B.V. All rights reserved.

DOI： 10.1016/j.jns.2016.01.018

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記述言語：英語   出版者・発行元：LIPPINCOTT WILLIAMS & WILKINS  

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Lippincott Williams and Wilkins  

DOI： 10.1212/WNL.0000000000002293

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：ELSEVIER SCIENCE BV  

A 59-year old man was admitted to our stroke care unit 1.8 hours after onset of cardioembolic stroke. Administration of issue-plasminogen activator achieved complete recanalization, and his lesion on diffusion-weighted imaging (DWI) disappeared and single photon emission computed tomography showed luxury perfusion. DWI reversal and luxury perfusion were sometimes observed in hyperacute stroke patients, especially timely reperfusion was achieved. However, the relationships between DWI reversal and luxury perfusion were not well known. Transient DWI reversal may be associated with luxury perfusion in patients treated with t-PA, via early complete recanalization achieved by thrombolysis.

DOI： 10.1016/j.jstrokecerebrovasdis.2015.09.017

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記述言語：英語   出版者・発行元：LIPPINCOTT WILLIAMS & WILKINS  

Limb-shaking associated with steno-occlusion of the internal carotid artery (ICA) was first reported by Miller Fisher(1) in 1962, and is characterized by brief, jerky, coarse, involuntary movements involving an arm or leg. Limb-shaking TIA is an under-recognized manifestation of an intracranial and extracranial carotid occlusion or severe stenosis. Although hemodynamic compromise has been suggested to be associated with shaking movements, the pathogenic nature of this symptom remains unclear. Neurophysiologic evaluation of this movement disorder would be useful, but the attack is rare and typically lasts less than 5 minutes.(2) Thus, few reports have investigated this hyperkinetic phenomenon under neurophysiologic assessment.(3&lt;/SUP)

DOI： 10.1212/WNL.0000000000002293

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：KARGER  

Background and Purpose: Hyperintense vessels (HV) detected on fluid-attenuated inversion recovery (FLAIR) in patients with acute ischemic stroke (AIS) indicate cerebral hypoperfusion. However, the clinical meaning of changes in HV is yet to be clarified. Here, we investigated serial changes to HV in patients with AIS who received tissue plasminogen activator (t-PA) therapy. Methods: We studied t-PA patients presenting with HV on FLAIR in the middle cerebral artery territory. Patients underwent brain MRI 1 h before and after t-PA infusion. HV scores (range 1-7) were evaluated according to Alberta Stroke Program Early Computed Tomography Score territories, and then by subtracting HV scores at 1 h after t-PA infusion from those on admission, with a result of &gt; 1 defined as decrease in HV score (DHV). Patients were divided into 2 groups based on the presence or absence of DHV. Multivariate logistic regression analysis was conducted to identify variables independently associated with good outcome (modified Rankin Scale score at 90 days after stroke onset of 0-1). Results: A total of 118 consecutive patients were enrolled (73 men; mean age 76 +/- 9.7; median initial National Institutes of Health Stroke Scale (NIHSS) 13; median initial HV score 5), of whom 52 (44%) had DHV. Patients with DHV showed a significantly lower NIHSS time course (p &lt; 0.001) and significantly smaller infarct volume time course (p &lt; 0.001) compared to those without DHV. Multivariate analysis showed that DHV was independently associated with good outcome (OR 3.89; 95% CI 1.55-9.77; p &lt; 0.01). The sensitivity and specificity of DHV for good outcome were 70 and 68%, respectively. Conclusion: A DHV on FLAIR predicts good outcome in patients receiving t-PA. (C) 2016 S. Karger AG, Basel

DOI： 10.1159/000443533

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：KARGER  

Background: The aim of the present study was to clarify the effect of glucose profiles after stroke, which was assessed by a continuous glucose monitoring (CGM) device. Methods: Acute ischemic stroke patients within 24 h of onset were prospectively studied. CGM was performed for 72 h after admission. CGM parameters were evaluated as follows: (1) mean glucose level, (2) area under the curve (AUC) for glucose level &gt;140 mg/dl and (3) SD of the glucose level. Infarct volume was measured at admission and 24 and 72 h after admission using diffusion-weighted imaging. CGM data and infarct volume growth were compared at 24 and 72 h. Results: Seventy-eight patients were enrolled in the present study. Spear man's rank correlation coefficients showed that both the mean glucose level (r = 0.433, p &lt; 0.001 for 24 h; r = 0.308, p = 0.006 for 72 h) and AUC &gt;140 mg/dl (r = 0.417, p &lt; 0.001 for 24 h; r = 0.277, p = 0.014 for 72 h) were significantly correlated with acute infarct volume growth. The SD of the glucose level was associated with infarct volume growth at 24 h (r = 0.303, p = 0.007), but not 72 h (r = 0.195, p = 0.088). Conclusion: Post-stroke hyperglycemia was associated with infarct volume growth during the acute phase of ischemic stroke. (C) 2016 S. Karger AG, Basel

DOI： 10.1159/000448329

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：ELSEVIER SCIENCE BV  

BACKGROUND: Because patients with warfarin-associated intracerebral hemorrhage (WAICH) have a high risk of ongoing bleeding, disability, and death, urgent coagulopathy reversal should be considered. On the other hand, thromboembolism may occur with reversal or withholding of anticoagulant therapy. The current status of acute hemostatic treatments and clinical outcomes in WAICH patients was investigated. METHODS: WAICH patients admitted within 3 days of onset were prospectively enrolled in 10 stroke centers. Thromboembolic and hemorrhagic complications and functional outcomes were followed-up for one year. RESULTS: Of 50 WAICH patients (31 men, 73 ± 9 years old) enrolled, all stopped warfarin on admission. Elevated prothrombin time-international normalized ratios (PT-INR) were normalized in 43 (86%). Anticoagulant therapy was resumed with intravenous full-dose unfractionated heparin followed by warfarin in 9 (18%), intravenous low-dose unfractionated heparin followed by warfarin in 14 (28%) and warfarin alone in 14 (28%) at a median of 2.5 (IQR 1.25-9), 4 (2-5.5) and 6 (3-11) days after onset, respectively, after emergent admission. Onset-to-admission time (per 1-hour increase; OR 0.55, 95% CI 0.19-0.84) was inversely associated with hematoma expansion. Anticoagulant therapy was resumed with intravenous full-dose unfractionated heparin in 9 (18%), low-dose heparin in 14 (28%) and warfarin alone in 14 (28%) at a median of 2.5, 4 and 6 days after onset, respectively. During one-year follow-up (n=47), 11 thromboembolic and 6 hemorrhagic complications were documented. Twenty four patients showed unfavorable outcomes, corresponding to a modified Rankin Scale score of 4-6. Thromboembolic complications (OR, 10.62; 95% CI, 1.05-227.85), as well as advanced age (per 1 year; OR, 1.27; 95% CI, 1.10-1.61) and higher National Institutes of Health Stroke Scale (NIHSS) score (per 1 point; OR, 1.24; 95% CI 1.07-1.55), were independently associated with unfavorable outcome. CONCLUSIONS: PT-INR normalization on admission and early anticoagulant resumption were common in WAICH patients. Thromboembolic complications were independently associated with unfavorable outcome.

DOI： 10.1016/j.jns.2015.10.031

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記述言語：日本語   出版者・発行元：(一社)日本神経学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：ELSEVIER SCIENCE BV  

Background: Cerebral small-vessel disease (SVD) is associated with renal dysfunction such as chronic kidney disease. Although cerebral microbleeds (CMBs) are common in patients with acute lacunar infarcts (ALI), the association between renal dysfunction and CMBs in such patients remains unclear. Methods: Between April 2007 and March 2013, we evaluated consecutive first-ever ALI patients, who were admitted to our hospital within 24 hours of stroke onset. CMBs were defined as focal areas of signal loss in brain parenchyma less than 5 mm on T2*-weighted gradient-echo imaging. Renal dysfunction was defined as an estimated glomerular filtration rate less than 60 mL/minute/1.73 m(2) on admission. Correlations between renal dysfunction and the presence (model 1) and location of CMBs (model 2; any deep or infratentorial CMBs) were determined by multivariable logistic regression analyses. Results: Among 152 patients (33.6% men; mean age, 67.6 years), 53 had CMBs. Patients with CMBs were older (69.9 versus 66.3 years, P = .03) and had a higher frequency of white matter hyperintensity (WMH; 62.3% versus 25.3%, P &lt; .001), silent lacunar infarcts (SLI; 75.5% versus 43.3%, P &lt; .001), and renal dysfunction (41.5% versus 22.2%, P = .015) than those without CMBs. On multivariable analyses, renal dysfunction (odds ratio, 95% confidence interval; model 1: 2.38, 1.02-5.66; model 2: 2.78, 1.16-6.81), WMH (3.87, 1.76-8.80; 3.72, 1.64-8.71), SLI (3.85, 1.71-9.14; 4.20, 1.77-10.8), and diabetes mellitus (. 26,.09-.63;.24,.08-.63) were independently associated with CMBs. Conclusions: In patients with ALI, renal dysfunction was positively associated with CMBs independent of cerebral SVD.

DOI： 10.1016/j.jstrokecerebrovasdis.2015.07.010

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：WILEY-BLACKWELL  

BACKGROUND: Large clinical trials are lack of data on non-vitamin K antagonist oral anticoagulants for acute stroke patients. AIM: To evaluate the choice of oral anticoagulants at acute hospital discharge in stroke patients with nonvalvular atrial fibrillation and clarify the underlying characteristics potentially affecting that choice using the multicenter Stroke Acute Management with Urgent Risk-factor Assessment and Improvement-NVAF registry (ClinicalTrials.gov NCT01581502). METHOD: The study included 1192 acute ischemic stroke/transient ischemic attack patients with nonvalvular atrial fibrillation (527 women, 77·7 ± 9·9 years old) between September 2011 and March 2014, during which three nonvitamin K antagonist oral anticoagulant oral anticoagulants were approved for clinical use. Oral anticoagulant choice at hospital discharge (median 23-day stay) was assessed. RESULTS: Warfarin was chosen for 650 patients, dabigatran for 203, rivaroxaban for 238, and apixaban for 25. Over the three 10-month observation periods, patients taking warfarin gradually decreased to 46·5% and those taking nonvitamin K antagonist oral anticoagulants increased to 48·0%. As compared with warfarin users, patients taking nonvitamin K antagonist oral anticoagulants included more men, were younger, more frequently had small infarcts, and had lower scores for poststroke CHADS2 , CHA2 DS2 -VASc, and HAS-BLED, admission National Institutes of Health stroke scale, and discharge modified Rankin Scale. Nonvitamin K antagonist oral anticoagulants were started at a median of four-days after stroke onset without early intracranial hemorrhage. Patients starting nonvitamin K antagonist oral anticoagulants earlier had smaller infarcts and lower scores for the admission National Institutes of Health stroke scale and the discharge modified Rankin Scale than those starting later. Choice of nonvitamin K antagonist oral anticoagulants was independently associated with 20-day or shorter hospitalization (OR 2·46, 95% CI 1·87-3·24). CONCLUSIONS: Warfarin use at acute hospital discharge was still common in the initial years after approval of nonvitamin K antagonist oral anticoagulants, although nonvitamin K antagonist oral anticoagulant users increased gradually. The index stroke was milder and ischemia-risk indices were lower in nonvitamin K antagonist oral anticoagulant users than in warfarin users. Early initiation of nonvitamin K antagonist oral anticoagulants seemed safe.

DOI： 10.1111/ijs.12452

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記述言語：英語   出版者・発行元：SPRINGER-VERLAG ITALIA SRL  

DOI： 10.1007/s10072-015-2128-y

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Lippincott Williams and Wilkins  

BACKGROUND AND PURPOSE: Blood pressure lowering is often performed as a part of general acute management in acute intracerebral hemorrhage (ICH) patients. The relationship between relative blood pressure reduction and clinical outcomes is not fully known. METHODS: Hyperacute (<3 h from onset) ICH patients with initial SBP more than 180 mmHg were included in the observational study. All patients received intravenous antihypertensive treatment based on a predefined protocol to lower and maintain SBP between 120 and 160 mmHg. The relative SBP reduction was defined as the ratio of SBP reduction to the admission SBP in the first 24 h, and associations between the relative SBP reduction and neurological deterioration (≥2 points decrease in the Glasgow Coma Scale score or ≥4 increase in the National Institutes of Health Stroke Scale score), hematoma expansion (>33% increase), and unfavorable outcome (modified Rankin scale score 4-6 at 3 months) were assessed with multivariate logistic regression analyses. RESULTS: Of the 211 patients [81 women, median age 65 (interquartile range 58-74) years, and median initial National Institutes of Health Stroke Scale score 13 (8-17)] enrolled, 17 (8%) showed neurological deterioration, 36 (17%) showed hematoma expansion, and 87 (41%) had an unfavorable outcome. On multivariate regression analyses, relative SBP reduction was independently and inversely associated with neurological deterioration (odds ratio 0.053, 95% confidence interval 0.011-0.254 per 10% increment), hematoma expansion (0.289, 0.099-0.841), and unfavorable outcome (0.254, 0.095-0.680) after adjusting for known predictive factors. CONCLUSION: Insufficient relative SBP reduction after standardized antihypertensive therapy in hyperacute ICH was independently associated with poor clinical outcomes. Aggressive antihypertensive treatment may improve clinical outcomes.

DOI： 10.1097/HJH.0000000000000512

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：ELSEVIER SCIENCE BV  

Valproic acid (VPA) is widely used for the clinical treatment of epilepsy. Previous studies have demonstrated that VPA ameliorates brain injury following experimental stroke. However, the effect of VPA in stroke models featuring comorbid conditions has not been fully explored. In this study, we investigate the effects of VPA on permanent ischemic stroke with hyperglycemia. Hyperglycemia Was induced by streptozotocin (STZ) injection 3 days before. Test animals received a single injection of VPA immediately after induction of ischemia. Control animals received occlusion and physiological saline injection, or STZ, occlusion, and saline. Magnetic resonance imaging of cerebral blood flow (CBF) and apparent diffusion coefficient (ADC) was performed 60 min after ischemia. Infarct volume, neurological deficits, rotarod test performance, and immunohistological markers were assessed 3 days after ischemia. Hyperglycemia significantly expanded the area of decreased of CBF and ADC, and increased the number of myeloperoxidase-positive cells, ionized calcium binding adapter molecule 1-positive cells, inducible nitric oxide synthase-positive cells, von Willebrand factor-positive cells, and Fluoro-Jade C-positive cells in the ischemic boundary zone, which was accompanied by increased infarct volume and deteriorated neurological deficit and rotarod test compared with normoglycemia (P &lt;0.05). VPA significantly alleviated the aggravation of functional outcome accompanied by suppressing these inflammation, endothelial injury, and neuronal degeneration compared with saline-treated group (P&lt;0.05). A single injection of VPA following permanent ischemia in STZ-induced hyperglycemic rats ameliorates neurological deficits and reduces neuronal degeneration by inhibiting inflammation and endovascular injury. VPA may be promising as a candidate therapy for human stroke. (C) 2015 Elsevier B.V. All rights reserved.

DOI： 10.1016/j.brainres.2015.02.013

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：JAPANESE CIRCULATION SOC  

Background: We conducted a multicenter retrospective cohort study to elucidate the characteristics of intracranial hemorrhage (ICH) in patients with atrial fibrillation treated with non-vitamin K antagonist oral anticoagulants (NOACs).
Methods and Results: We sent a questionnaire to the directors of 241 stroke centers in Japan to establish the clinical characteristics of NOAC-associated cerebral hemorrhage (CH), including hematoma size, hematoma enlargement (HE) and in-hospital mortality of patients treated in their institutions. We undertook a literature review to establish the clinical characteristics of warfarin-associated CH and compared these with our data. We received 174 responses (72.2%), of which 67 (38.5%) gave anonymous details of 130 eligible patients (male, 67.7%; mean age, 77.3 +/- 8.3 years, in-hospital mortality rate, 11.5%). We judged that 87 of the 130 patients had presented with CH: one-fifth had taken antiplatelet drugs. We found that the incidences of HE and mortality in the 87 patients presenting with NOAC-associated CH were lower than would have been expected in those with warfarin-associated CH (17% vs. 26%, and 16% vs. 35%, respectively).
Conclusions: More than half the stroke center directors who responded to our questionnaire had not experienced cases of NOAC-associated ICH. Compared with warfarin, NOACs appear to present a lower risk of HE and death in patients with atrial fibrillation who develop CH.

DOI： 10.1253/circj.CJ-14-1209

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記述言語：英語   出版者・発行元：LIPPINCOTT WILLIAMS & WILKINS  

DOI： 10.1111/ijs.12452

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：WILEY-BLACKWELL  

Rationale and aimsMonotherapy with antiplatelet agents is only modestly effective in secondary prevention of ischemic stroke (IS), particularly in patients with multiple risk factors such as cervicocephalic arterial stenosis, diabetes, and hypertension. While dual antiplatelet therapy (DAPT) with aspirin and clopidogrel reduced IS recurrence, particularly in the early stages after IS, it increased the risk of bleeding. Compared with aspirin, cilostazol prevented IS recurrence without increasing the incidence of serious bleeds. In patients with intracranial arterial stenosis, no significant increase in bleeding events was observed for DAPT with cilostazol and aspirin, compared to that for aspirin monotherapy. DAPT involving cilostazol may therefore be safer than conventional DAPT. These findings prompted us to conduct the Cilostazol Stroke Prevention Study for Antiplatelet Combination (; identifier: NCT01995370) to evaluate the safety and efficacy of DAPT involving cilostazol for secondary IS prevention, in comparison with that of antiplatelet monotherapy.
DesignThe is a multicenter, randomized, open-label, parallel-group trial. A total of 4000 high-risk patients with noncardioembolic IS will be randomized 8-180 days after onset to receive aspirin or clopidogrel monotherapy, or DAPT with cilostazol and aspirin or clopidogrel for at least one-year.
Study outcomesThe primary outcome is IS recurrence. Secondary outcomes are composite occurrences of any stroke, death from any cause, myocardial infarction, vascular death, and other vascular events.
DiscussionThe is expected to provide evidence indicating whether secondary IS prevention in high-risk patients can be improved by using DAPT involving cilostazol.

DOI： 10.1111/ijs.12420

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：ELSEVIER SCIENCE BV  

BACKGROUND: The effect of renal dysfunction on intracerebral hemorrhage (ICH) remains unclear. We investigated associations of renal dysfunction assessed by estimated glomerular filtration rate (eGFR) with clinical courses and outcomes in ICH patients. METHODS: From a prospective, multicenter, observational study, 203 patients who had supratentorial ICH within 3 hours of onset were included. Patients were classified into 3 groups based on eGFR: Group 1 (eGFR < 60 mL/minute/m(2)), Group 2 (60-89), and Group 3 (≥ 90). Outcomes included neurologic deterioration within 72 hours, hematoma expansion (> 33% in volume) at 24 hours, and favorable (modified Rankin Scale [mRS] ≤ 2) or unfavorable (mRS ≥ 5) outcome at 3 months. RESULTS: Thirty-seven patients (16 women, 74.6 ± 13.2 years) were assigned to Group 1, 99 (34 women, 65.2 ± 11.4 years) to Group 2, and 67 (30 women, 61.3 ± 9.4 years) to Group 3. Significant differences were found in age (P < .001) and initial systolic blood pressure among the groups (208.4 ± 18.0, 201.9 ± 15.1, and 198.1 ± 14.2 mm Hg for Group 1, 2, and 3, respectively; P = .006). Similar rates of neurologic deterioration (14%, 6%, and 6%) and hematoma expansion (16%, 14%, and 18%) were observed among the groups. However, in Group 1, favorable outcome was less frequent (17%, 48%, and 42%; P = .002) and unfavorable outcome was more frequent (24%, 7%, and 6%; P = .013) than in the other groups. After adjustment for confounders, eGFR < 60 mL/minute/m(2) was independently associated with both favorable outcome (odds ratio [OR], .21; 95% CI, .07-.54) and unfavorable outcome (OR, 5.64; 95% CI, 1.80-18.58). CONCLUSIONS: Renal dysfunction (eGFR < 60 mL/minute/m(2)) was associated with poor clinical outcome after ICH.

DOI： 10.1016/j.jstrokecerebrovasdis.2014.08.015

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：ELSEVIER SCIENCE BV  

Background: Half of acute stroke patients have poor outcomes at 3 months even when treated with intravenous thrombolysis using tissue-plasminogen activator (t-PA) therapy. The aim of the present study was to evaluate the impact of the susceptibility vessel sign (SVS) on magnetic resonance imaging (MRI) T2* at the proximal portion of the middle cerebral artery (M1 proximal SVS) on clinical outcome in anterior circulation stroke patients treated with t-PA.
Methods: The presence of the M1 proximal SVS was assessed before t-PA therapy. Good outcome and poor outcome at 3 months were defined as a modified Rankin Scale score of 0 to 2 and 4 to 6, respectively. The predictive values of the M1 proximal SVS for a good and poor outcome were calculated.
Results: 161 patients (median age [interquartile], 76 [67-83] years; male, 91 [57%]) were enrolled. At 3 months after stroke, 68 (42%) patients achieved a good outcome, and 75 (47%) had a poor outcome. The M1 proximal SVS was found in 17 (11%) patients, of whom none (0%) achieved a good outcome, and 16 (94%) had a poor outcome. The sensitivity and positive predictive value of the M1 proximal SVS for good outcome were very low (0.000 and 0.000, respectively). Furthermore, the specificity and positive predictive value of the M1 proximal SVS for poor outcome were very high (0.988 and 0.941, respectively).
Conclusion: The M1 proximal SVS appears to be a strong predictor for poor outcome after t-PA therapy. (C) 2014 Elsevier B.V. All rights reserved.

DOI： 10.1016/j.jns.2014.12.002

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：JAPAN SOC INTERNAL MEDICINE  

Objective The significance of early mild clinical improvement after intravenous tissue plasminogen activator (IVtPA) treatment is unclear. Therefore, we examined whether the timing of clinical improvement after IVtPA predicted the clinical outcome at 3 months.
Methods Consecutive patients with acute cerebral infarction in the anterior circulation who received IVtPA treatment within 3 hours of the onset of symptoms were enrolled in the study. Patients were classified according to the timing of clinical improvement [early responder (ER), National Institutes of Health Stroke Scale (NIHSS) score improved &gt;= 4 points or who had a score of 0 within 2 hours after IVtPA; late responder (LR), a similar improvement between 2 and 24 hours; and non-responder (NR)] and according to the arterial occlusion site (P group, internal carotid artery and proximal middle cerebral artery M1 region; and D group, distal M1 and M2).
Results Ninety-three patients [median age, 74 (67-79) years; 54 men (58%); median NIHSS score, 11 (7-16)] were enrolled in the study. The P group consisted of 48 (52%) patients and the D group consisted of 45 (48%) patients. Thirty-eight patients (41%) were classified as ERs, 20 (22%) as LRs, and 35 (38%) as NRs. On a multivariate regression analysis, the P group [odds ratio (OR), 3.24; 95% confidence interval (CI), 1.08-10.45; p=0.036] and NR (OR, 4.04; 95% CI, 1.29-14.27; p=0.016) were independent predictors of a poor outcome. ER (47%, p=0.01) and LR (45%, p=0.01) patients showed fewer poor outcomes than NR (77%) patients, but the rate did not differ significantly between the ER and LR patients.
Conclusion Early mild clinical recovery did not predict a good outcome. The occlusion site was a stronger predictor of clinical improvement after IVtPA administration.

DOI： 10.2169/internalmedicine.54.4990

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：S. Karger AG  

Introduction: Levodopa (LD) is important in the clinical treatment of Parkinson's disease (PD), and the changes of its pharmacokinetics may affect the clinical outcome. LD is mainly absorbed in the upper intestine
thus, the pharmacokinetics of LD may change after gastrointestinal operation. Here, we present the case of a patient who underwent resection of the intestine and compared his LD pharmacokinetics before and after resection. Case Presentation: A 72-year-old Japanese male PD patient developed jaundice and was diagnosed with cholangiocarcinoma. Pancreaticoduodenectomy was performed and part of the stomach, total duodenum, and part of the jejunum were resected. The patient had been treated with LD, and his pharmacokinetics was checked twice at the age of 68 years. Because LD is absorbed in the duodenum and jejunum, we checked his pharmacokinetics again after the operation. The results before the operation were almost similar
however, in comparison, the area under the curve and peak drug concentration was reduced, and the time-to-peak drug concentration and elimination halftime were elongated after the operation. Conclusion: Physicians must pay attention to the change of LD pharmacokinetics after gastrointestinal operation.

DOI： 10.1159/000381181

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Diagnosing clinical progressive supranuclear palsy (PSP) is challenging. We hypothesize that there are more cases of pathological PSP than have been clinically identified, but its diagnosis is challenging because the initial lesions and progression of PSP have not yet been clarified. The purpose of our study was to clarify the incidence of PSP in consecutive autopsy cases and identify pathological characteristics of early PSP. We investigated 324 consecutive autopsy patients from a general geriatric hospital (age, mean±SD=82.5±8.7 years). Paraffin sections of the midbrain were immunostained with anti 4-repeat tau antibodies (RD4). We selected cases showing RD4-positive neurofibrillary tangles and tufted astrocytes in the midbrain sections. Then, we used anti-phosphorylated tau antibody to immunostain sections from the basal ganglia, subthalamic nucleus, midbrain, pons, medulla, and cerebellum. Of the 324 patients, 35 had RD4-positive structures in the midbrain. From these 35 cases, we excluded those for which autopsies confirmed definite PSP (n=5) and cases of corticobasal degeneration (n=1), Alzheimer's disease (n=11), dementia of grain (n=10), and neurofibrillary tangles predominant forms of senile dementia (n=2), leaving 8 cases. We diagnosed these 8 cases as pure PSP-type tauopathy. Pure PSP-type tauopathy was detected in 2.5% of the consecutive autopsy cases, and this incidence was 1.6 times greater than that of neuropathologically definite PSP. This pure PSP-type tauopathy likely indicates preclinical stages of PSP. Furthermore, the novel neuropathological finding, which we term "preclinical PSP," is unique and has not previously been reported. In order to elucidate the causes and pathological mechanisms of PSP, preclinical PSP should be investigated further.

DOI： 10.1272/jnms.82.266

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：JAPAN SOC INTERNAL MEDICINE  

We herein report a case of ischemic stroke in a 69-year-old man with unilateral moyamoya vessels originating from the proximal portion of the left middle cerebral artery. In addition, digital-subtraction angiography demonstrated a string-of-beads-like appearance in the cavernous portion of the left internal carotid artery. A genetic analysis revealed a heterozygous c.14576G&gt;A variant in ring finger protein 213. The patient's younger brother had a history of hemorrhagic stroke and had been diagnosed with moyamoya disease. We finally considered that the unilateral moyamoya vessel and string-of-beads appearance observed in the current case were not simply caused by atherosclerosis, but rather represented symptoms within the moyamoya spectrum.

DOI： 10.2169/internalmedicine.54.3534

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記述言語：英語  

DOI： 10.1016/j.jns.2014.10.019

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1111/ijs.12360

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：ELSEVIER SCIENCE BV  

Objective: We investigated whether brain natriuretic peptide (BNP) levels could be used as a marker to predict recurrent stroke in ischemic stroke survivors.
Methods: From April 2007 to March 2011, consecutive patients within 24 h of onset of ischemic stroke were prospectively enrolled, and admission plasma BNP levels were measured. Survivors were followed up to 12 months after stroke onset. Patients were divided into two groups: the recurrence group and the non-recurrence group. Factors associated with stroke recurrence were investigated by multiple logistic regression analysis.
Results: A total of 793 patients who were alive at hospital discharge were included; 42(5%) patients had recurrent stroke. There were no differences in BNP levels between groups. With respect to 257 patients with atrial fibrillation (AF), BNP levels were significantly higher in the recurrence group than in the non-recurrence group (426.0 vs. 192.0 pg/mL, P = 0.0007). The optimal cutoff level, sensitivity, and specificity of BNP levels to distinguish the recurrence group from the non-recurrence group were 300.0 pg/mL, 80%, and 73%, respectively. After adjustment for age and sex, plasma BNP &gt;= 300.0 pg/mL (OR, 9.2; 95% Cl, 1.87-45.01, P = 0.0062) was found to be independently associated with recurrent stroke in stroke survivors with AF.
Conclusion: Admission BNP levels can predict recurrent stroke in stroke survivors with AF. (C) 2014 Elsevier B.V. All rights reserved.

DOI： 10.1016/j.clineuro.2014.09.028

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記述言語：日本語   出版者・発行元：(NPO)日本脳神経血管内治療学会  

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記述言語：日本語   出版者・発行元：(NPO)日本脳神経血管内治療学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：ELSEVIER SCIENCE BV  

Background: Whether brain natriuretic peptide (BNP) levels are associated with early recurrent stroke in cardioembolic stroke patients was investigated. Methods: From January 2010 to March 2014, consecutive patients within 24 hours of onset of cardioembolic stroke were prospectively enrolled, and admission plasma BNP levels were measured. Recurrent stroke was identified as the occurrence of additional neurologic deficits and the appearance of a new infarct on neuroimaging. Patients were divided into 2 groups: the recurrence group and the nonrecurrence group. Factors associated with stroke recurrence were investigated by multiple logistic regression analysis. Results: A total of 348 patients were included; 17 patients (5%) had recurrent stroke during hospitalization. The median interval from stroke onset to recurrent stroke was 4 days (range, 0-30). BNP levels were significantly higher in the recurrence group than in the nonrecurrence group (304.1 vs. 206.5 pg/mL, P 5.029). The optimal cutoff level, sensitivity, and specificity of BNP levels to distinguish the recurrence group from the nonrecurrence group were 255.0 pg/mL, 76%, and 60%, respectively. On multivariate analysis after adjustment for confounders, plasma BNP &gt;= 255.0 pg/mL (odds ratio, 5.21; 95% confidence interval, 1.63-16.72; P = .005) was independently associated with recurrent stroke during hospitalization in cardioembolic stroke patients. Conclusions: Plasma BNP could be a useful marker for predicting early recurrent stroke during hospitalization in cardioembolic stroke patients.

DOI： 10.1016/j.jstrokecerebrovasdis.2014.06.003

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：KARGER  

Background: Intravenous thrombolysis using the tissue-type plasminogen activator (t-PA) is contraindicated for patients with a history of intracerebral hemorrhage (ICH). T2*-weighted magnetic resonance imaging (MRI) is able to detect asymptomatic ICH. If there is an association between asymptomatic ICH on T2* before t-PA therapy and ICH after t-PA therapy, we may be able to take preventive measures before starting t-PA therapy in patients with MRI-proven hemorrhage. The aim of the present study was to investigate whether asymptomatic ICH seen on T2* increases the risk of new ICH after t-PA therapy. Methods: Patients who had consecutive stroke treated with t-PA between October 2005 and November 2013 were enrolled. A hypointense T2* signal with a diameter &gt;5 mm was defined as asymptomatic ICH before t-PA therapy. The presence of new ICH at 24 h after t-PA therapy was assessed using T2*. Symptomatic ICH (sICH) was defined as new ICH combined with an increase in the National Institutes of Health Stroke Scale score &gt;= 4. At 3 months after onset, good and poor outcomes were defined as modified Rankin Scale (mRS) scores of 0-1 and 4-6, respectively. Results: Of 300 patients (age 77 [68-83] years; 173 [58%] males), 25 (8%) had an asymptomatic ICH on T2* before t-PA therapy. Eleven (45%) patients showed an isolated asymptomatic ICH. Three (12%) patients had a round hypointense lesion similar to microbleeds. Nine (36%) patients had a hemorrhagic transformation within a prior infarcted area. Multiple asymptomatic ICHs were seen in 2 (8%) patients. The rates of good and poor outcomes at 3 months were 24 and 59% of patients with asymptomatic ICH and 38 and 41% of patients without asymptomatic ICH (p = 0.300 and 0.202, respectively). At 24 h after t-PA therapy, 11 (44%) of the 25 patients with asymptomatic ICH before t-PA therapy and 87 (32%) of 275 without asymptomatic ICH had new ICH (p = 0.265). Only 1 (4%) of 25 patients with asymptomatic ICH before t-PA therapy and 6 (2%) of 275 without asymptomatic ICH had sICH within 24 h (p = 0.460). On multivariate logistic regression analysis, neither new ICH (odds, 1.19; 95% CI, 0.40-3.54, p = 0.753) nor sICH (odds, 0.95; 95% CI, 0.08-11.90, p = 0.970) was related to asymptomatic ICH on T2* before t-PA therapy. Conclusion: The presence of T2* hypointensity as a marker of asymptomatic ICH may not be associated with new ICH and sICH after t-PA therapy. (C) 2014 S. Karger AG, Basel

DOI： 10.1159/000365207

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：LIPPINCOTT WILLIAMS & WILKINS  

BACKGROUND AND PURPOSE: The associations between early blood pressure (BP) variability and clinical outcomes in patients with intracerebral hemorrhage after antihypertensive therapy, recently clarified by a post hoc analysis of Intensive Blood Pressure Reduction in Acute Cerebral Hemorrhage Trial 2 (INTERACT2), were confirmed using the Stroke Acute Management with Urgent Risk-factor Assessment and Improvement (SAMURAI)-intracerebral hemorrhage study cohort. METHODS: Patients with hyperacute (<3 hours from onset) intracerebral hemorrhage with initial systolic BP (SBP) >180 mm Hg were registered in a prospective, multicenter, observational study. All patients received antihypertensive therapy based on a predefined standardized protocol to lower and maintain SBP between 120 and 160 mm Hg using intravenous nicardipine. BPs were measured hourly during the initial 24 hours. BP variability was determined as SD and successive variation. The associations between BP variability and hematoma expansion (>33%), neurological deterioration within 72 hours, and unfavorable outcome (modified Rankin Scale, 4-6) at 3 months were assessed. RESULTS: Of the 205 patients, 33 (16%) showed hematoma expansion, 14 (7%) showed neurological deterioration, and 81 (39%) had unfavorable outcomes. The SD and successive variation of SBP were 13.8 (interquartile range, 11.5-16.8) and 14.9 (11.7-17.7) mm Hg, respectively, and those of diastolic BP were 9.4 (7.5-11.2) and 13.1 (11.2-15.9) mm Hg, respectively. On multivariate regression analyses, neurological deterioration was associated with the SD of SBP (odds ratio, 2.75; 95% confidence interval, 1.45-6.12 per quartile) and the successive variation of SBP (2.37; 1.32-4.83), and unfavorable outcome was associated with successive variation of SBP (1.42; 1.04-1.97). Hematoma expansion was not associated with any BP variability. CONCLUSIONS: SBP variability during the initial 24 hours of acute intracerebral hemorrhage was independently associated with neurological deterioration and unfavorable outcomes. Stability of antihypertensive therapy may improve clinical outcomes.

DOI： 10.1161/STROKEAHA.114.005420

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：ELSEVIER SCIENCE BV  

Background and purpose: The aim of the present study was to devise a simple grading scale for assessing the risk of development of malignant MCA infarction (MMI).
Methods: Using MRI, patients with MCA infarction and proximal vessel occlusion (ICA or M1) within 24 h of onset were retrospectively studied. MMI was defined as clinical deterioration, midline shift &gt;= 5 mm, or brain herniation within 48 h of admission. We evaluated clinical factors independently associated with MMI and created a simple score according to the multivariate logistic regression analysis.
Results: Subjects comprised 119 patients, 57 of which (47.9%) developed MMI. Multivariate logistic regression analysis revealed the following independent factors associated with MMI: DWI ASPECTS &lt;= 3 [odds ratio (OR), 4.16; 95% Cl, 136-12.66, P = 0.012], ACA territory involvement [OR, 6.90; 95% confidence interval [CI], 2.06-23.10, P = 0.002], M1 susceptibility vessel sign (SVS) on T2*-gradient echo [OR, 4.55; 95% Cl, 1.38-14.98, P = 0.013], and hyperglycemia (glucose value &gt;= 145 mg/dl) [OR, 531; 95% Cl, 1.80-15.68, P = 0.002]. These four variables were selected for use in the DASH score, with DWI ASPECTS &lt;= 3 as 1 point, ACA territory involvement as 1 point, M1 SVS as 1 point, and hyperglycemia as 1 point. The likelihood of developing MMI for each score was as follows: score 0, 9.1%; score 1, 20.5%; score 2, 63.0%; score 3-4, 96.8%. The C statistic for the score was 0.88 (95% Cl, 0.82-0.94, P &lt; 0.001).
Conclusion: Our DASH score reliably assessed a risk for development of MMI in large MCA infarctions. (C) 2014 Elsevier B.V. All rights reserved.

DOI： 10.1016/j.jns.2013.12.024

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：ELSEVIER SCI LTD  

Previous reports have shown that plasma brain natriuretic peptide (BNP) levels are increased in patients with subarachnoid hemorrhage and ischemic stroke. We examined BNP in patients with intracerebral hemorrhage (ICH). Between June 2006 and February 2010, we prospectively enrolled consecutive patients with acute ICH within 24 hours of onset. The plasma BNP level was measured twice, on admission and 4 weeks after onset or at discharge. We investigated whether plasma BNP was elevated in the acute phase of ICH and associated factors. The mean standard deviation (SD) plasma BNP level of all patients was 71.1 +/- 104.1 pg/mL. The log BNP level positively correlated with the cardio-thoracic ratio (r = 0.240, p = 0.0001). Moreover, BNP was significantly associated with intraventricular extension (p = 0.0039) and hydrocephalus (p = 0.0046). The mean SD BNP level of patients with cerebellar hemorrhage was the highest (130.2 +/- 152.0 pg/mL), followed by brainstem (84.5 +/- 170.6 pg/mL), lobar (72.4 +/- 148.1 pg/mL), thalamus (64.8 +/- 72.1 pg/mL), and putamen (59.9 +/- 62.6 pg/mL) hemorrhages. In 185 patients, BNP was measured in the subacute phase of ICH. The BNP level in the acute phase of ICH was significantly higher than that in the subacute phase of ICH (69.3 +/- 108.1 versus 21.7 +/- 23.5 pg/mL, p &lt; 0.0001). In conclusion, plasma BNP appears to be elevated in the acute phase of ICH, particularly in those with cerebellar lesions. (C) 2013 Elsevier Ltd. All rights reserved.

DOI： 10.1016/j.jocn.2013.02.035

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：ELSEVIER SCIENCE BV  

Background: The purpose of this study was to examine the frequency and characteristics of re-exacerbation of stroke symptoms within 24 hours after tissue plasminogen activator (t-PA) infusion. Methods: We studied consecutive stroke patients treated with t-PA within 3 hours of onset of symptoms admitted between October 2005 and March 2010. We divided patients into 4 groups: improvement (IM; improvement in National Institutes of Health Stroke Scale [NIHSS] &gt;= 4 points), unchanged (UN; no change or decline in NIHSS &lt;4 points), exacerbation (EX; decline in NIHSS &gt;= 4 points), and re-exacerbation (RE-EX; decline of NIHSS &gt;= 4 points accompanied by re-exacerbation of neurologic symptoms in NIHSS &gt;= 4 points). We compared clinical characteristics among the 4 groups. Results: Two hundred twenty-two patients (135 men; median age 76 years) were enrolled. Sixteen of the 222 (7%) were in the RE-EX group. Small vessel disease (SVD), hemorrhagic cerebral infarction, and reocclusion were significantly more common among patients in the RE-EX group. SVD, hemorrhagic cerebral infarction, and reocclusion occurred in 44%, 25%, and 13% of patients in the RE-EX group, in 9%, 22%, and 0% of patients in the EX group, in 5%, 6%, and 0% of patients in the IM group, and in 17%, 14%, and 1% of patients in the UN group, respectively (P &lt; .001, P = .041, and P &lt; .001). Multivariate logistic regression analysis revealed that SVD was the only independent factor associated with re-exacerbation within 24 hours after t-PA infusion (odds ratio 3.52; 95% confidence interval [CI] 1.19-10.40; P = .023). Conclusions: Seven percent of patients re-exacerbated within 24 hours after intravenous infusion of t-PA. Re-exacerbation within 24 hours after t-PA infusion was strongly associated with SVD.

DOI： 10.1016/j.jstrokecerebrovasdis.2012.09.009

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：ELSEVIER SCIENCE BV  

This study compared the detection rate of ischemic lesions within 3 hours of onset by computed tomography (CT) and diffusion-weighted magnetic resonance imaging (DWI). The study group comprised 130 patients (71 men; median age, 75 years) with an anterior territory stroke who underwent CT and DWI within 3 hours of onset. The lesions revealed on CT and DWI were assessed using the CT-Alberta Stroke Program Early CT Score (ASPECTS) and DWI-ASPECTS, and detection rates were compared for each ASPECTS region. The detection rate of ischemic lesions was higher on DWI than on CT (76.9% v 30.0%; P &lt; .001). The DWI-ASPECTS score was not correlated with the CT-ASPECTS score (r = 0.51; P &lt; .001). Ischemic lesions were detected in the insula (59.2% for DWI vs 15.4% for CT; P &lt; .001), lentiform nucleus (43.8% v 20.0%; P &lt; .001), and the M1 (30.8% v 6.9%, P &lt; .001), M2 (50.8% v 6.2%; P = .006), M3 (28.5% v 3.1%; P = .006), M4 (32.3% v 6.9%; P &lt; .001), M5 (48.5% v 10.8%; P &lt; .001), and M6 (31.5% v 4.6%, P = .012) areas of the middle cerebral artery. DWI detected ischemic lesions significantly more frequently than CT in all ASPECTS regions except the caudate head and internal capsule.

DOI： 10.1016/j.jstrokecerebrovasdis.2012.08.014

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：KARGER  

Background and Purpose:The purpose of the present study was to test the hypothesis that plasma brain natriuretic peptide (BNP) is associated with short-term mortality after intracerebral hemorrhage (ICH). Methods: We prospectively enrolled 271 patients (median age 72 years; 109 females) who were admitted within 24 h of ICH onset between April 2007 and July 2011 and in whom plasma BNP levels were measured upon admission. The patients were assigned to two groups according to survival within 1 month of ICH. Factors associated with mortality were determined by multivariate logistic regression analysis. Results: Within 1 month of ICH, 48(17.7%) of the 271 enrolled patients died. The median (interquartile range) level of plasma BNP was significantly higher in the group of non-survivors than in the group of survivors [102.5(48.7-205.0) vs. 32.4(17.3-85.0) pg/ml; p &lt; 0.001]. A cutoff BNP level of 60.0 pg/ml could predict death within 1 month of ICH. Multivariate logistic regression analysis showed that a plasma BNP of &gt;60.0 pg/ml (OR 4.7; 95% CI 1.43-15.63; p = 0.011) was independently associated with mortality within 1 month after ICH. Conclusions: A high BNP level upon admission is associated with mortality within 1 month after ICH. (C) 2014 S. Karger AG, Basel

DOI： 10.1159/000356198

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記述言語：日本語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Societas Neurologica Japonica  

Transient neurological attacks (TNAs) are attacks with temporary (&lt
24 h) neurological symptoms, and reported in 1975. Ischemic cerebral infarction often occurres after transient neurological symptoms which are not sometimes involved in transient ischemic attack (TIA) criteria. The purpose of this study was to clarity transient neurological symptoms before the onset of ischemic stroke. Consecutive acute stroke and TIA patients within 7 days of onset between July 2011 and December 2012 were studied. Questionnaire survey of transient neurological symptoms was done and we investigated the history of transient neurological symptoms and divided the patients into three groups, TIA group (history of TIA), TNAs group (history of TNAs), and no past history group. We compared clinical characteristics, the rate of posterior circulation lesions, and number of attacks among three groups. 184 patients (male 112 patients, mean 73 years old) were enrolled into the present study. TNAs group had 13 (7%) patients, and TIA had 20 (11%). Neurological symptoms of TNAs group were 5 (38%) transient dizziness, 3 (23%) disturbance of consciousness, 2 (23%) weakness of legs, 1 (8%) sensory disturbance of legs, 1 (8%) gait disturbance, and 1 (8%) sensory disturbance of lips. Five (38%) TNAs group had multiple attacks. In 33 transient neurological symptom patients, 17 (52%) patients did not have hospital visit, and 7 (21%) patient did not have antiplatelet and anticoagulant drug. TNAs group more frequently had hyperlipidemia, diabetes mellitus, and posterior circulation lesions among three groups. 20% posterior circulation lesion patients had TNAs history, and posterior circulation might be examined in TNAs patients.

DOI： 10.5692/clinicalneurol.54.480

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記述言語：日本語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Societas Neurologica Japonica  

The frequency and clinical characteristics of intractable hiccups due to the medullary infarction is unknown. The aim of this study was to identify the lesions of hiccups using by brain MRI. Ninety acute medullary patients admitted to our stroke center within 14 days of stroke onset between April 2004 and August 2012 were retrospectively studied. We evaluated clinical characteristics and the frequency of the patients causing intractable hiccups among acute medullary stroke patients. We divided the patients into two groups, intractable hiccups group, and not hiccups group. Of 90 patients, five (5.5%) had intractable hiccups. Hiccups group had more frequently involved right middle medullary lesion than not hiccups group (hiccups group vs. not hiccups group
(60% vs. 4%, p &lt
0.001). In 16 cases reported the lesion of intractable hiccups, the right middle medullary lesion was 11 cases. We suspected that the lesion of the intractable hiccups was associated with the right middle medullary.

DOI： 10.5692/clinicalneurol.54.403

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Background: The therapeutic efficacy of low-dose intravenous alteplase (0.6 mg/kg) for basilar artery occlusion (BAO) remains unknown. Methods: BAO patients enrolled from the Japanese multicenter registry involving 600 stroke patients treated with the low-dose intravenous alteplase were studied. Results: Twenty-five patients had BAO (8 women ranging from 32-92 years of age
mean baseline National Institutes of Health Stroke Scale [NIHSS] score 16). The stroke subtype was cardioembolic in 15 patients and atherothrombotic in 4 patients. BAO was recanalized during hospitalization in 18 (78%) of 23 patients undergoing follow-up angiography. Within the initial 24 hours, 14 patients (56%) had a ≥8-point decrease in the NIHSS score, being more common than 267 patients with middle cerebral artery occlusion (MCO) from the same registry (odds ratio [OR] 2.50
95% confidence interval [CI] 1.06-5.97) after adjustment by sex, age, and baseline NIHSS score. In addition, 4 patients (16%) had a ≥4-point increase in the score, being marginally more common than MCO patients (OR 3.13
95% CI 0.81-10.25). Symptomatic intracranial hemorrhage within the initial 36 hours (8% v 5%), independence at 3 months (modified Rankin Scale score ≤2, 48% v 52%), and mortality at 3 months (4% v 6%) were similar when comparing BAO and MCO patients. When compared with previous studies of BAO, vital and functional outcomes at 3 months were relatively better in our study. Conclusions: The use of low-dose alteplase resulted in similar outcomes when comparing acute BAO and MCO patients. © 2013 by National Stroke Association.

DOI： 10.1016/j.jstrokecerebrovasdis.2012.08.013

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：LIPPINCOTT WILLIAMS & WILKINS  

Background and Purpose It is unknown whether new-extraischemic microbleeds (new-EMBs) develop rapidly after tissue-type plasminogen activator (tPA) infusion. We hypothesized that new-EMBs may develop rapidly after tPA infusion using T2*-weighted MRI (T2*) and investigated the frequency and clinical factors associated with new-EMBs.
Methods Patients with acute stroke within 3 hours of onset who were treated with tissue-type plasminogen activator (tPA) were studied prospectively. T2* was performed before and 24 hours after tPA therapy. Independent clinical factors associated with new-EMBs development were examined using multivariate logistic regression analysis.
Results A total of 224 patients (121 men; mean age, 76.210.6 years) were enrolled in the present study. MBs before tPA infusion were observed in 72 (32.1%) patients. Within 24 hours after tPA infusion, 6 (2.7%) patients had symptomatic intracranial hemorrhage (extraischemic [n=4], and hemorrhagic transformation [n=2]). Follow-up T2* revealed asymptomatic new-EMBs in 11 (4.9%) patients and hemorrhagic transformation in the infarcted area in 65 (29.0%). The total and mean number of new-EMBs were 23 and 1.6 +/- 1.3, respectively. Patients with new-EMBs more frequently had symptomatic extraischemic hemorrhage than those without new-EMBs (27.3% [3/11] versus 0.5% [1/213]; P=0.0003). However, the frequency of hemorrhagic transformation was not different between patients with and without new-EMBs (27.3% versus 29.1%; P=0.9999). Multivariate logistic regression demonstrated that the presence of MBs before tPA infusion was the only independent factor associated with new-EMBs (odds ratio, 10.6; 95% confidence interval, 20.68-54.279; P=0.0046).
Conclusions New-EMBs occurred rapidly after tPA infusion in 4.9% of patients. The presence of MBs before tPA therapy was associated with new-EMBs. Patients with new-EMBs are likely to have symptomatic extraischemic hemorrhage.

DOI： 10.1161/STROKEAHA.113.001778

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：ELSEVIER SCIENCE BV  

Background and purpose: The aim of this study was to investigate whether early initiation of new oral anticoagulants (NOAC) for acute stroke or transient ischemic attack (TIA) patients with nonvalvular atrial fibrillation (NVAF) are safe.
Methods: Between March 2011 and September 2012, stroke or TIA patients with NVAF who started NOAC within 2 weeks were enrolled retrospectively. Symptomatic intracerebral hemorrhage (ICH), hemorrhagic transformation (HT) on T2*-weighted MRI, recurrence of stroke or TIA, systemic embolism and any bleeding complications after initiation of NOAC were evaluated.
Results: 41 patients (25 males; mean age 76.2 years) started NOAC; of which, 39(95%) patients had stroke, and 2 (5%) had TIA. The median (interquartile range) interval from onset to treatment with NOAC was 2 (1-6) days. Symptomatic ICH was not observed. HT on initial T2* and new HT on follow-up T2* were 5 (12%) and 11 (31%), but it was asymptomatic. Of 5 patients who had HT on the initial T2*, enlargement of hemorrhage on follow-up T2* (hemorrhagic infarction (HI) Type 1 -&gt; HI Type 2) was observed in 1 patient, but it was asymptomatic. None of the patients had recurrent stroke or TIA, systemic embolism, and any bleeding complications.
Conclusions: The NOAC may be safe in acute stroke or TIA patients with NVAF. A large, prospective study is needed to confirm this. (C) 2013 Elsevier B.V. All rights reserved.

DOI： 10.1016/j.jns.2013.05.016

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：LIPPINCOTT WILLIAMS & WILKINS  

BACKGROUND AND PURPOSE: Blood pressure (BP) lowering is often conducted as part of general acute management in patients with acute intracerebral hemorrhage. However, the relationship between BP after antihypertensive therapy and clinical outcomes is not fully known. METHODS: Hyperacute (<3 hours from onset) intracerebral hemorrhage patients with initial systolic BP (SBP) >180 mm Hg were included. All patients received intravenous antihypertensive treatment, based on predefined protocol to lower and maintain SBP between 120 and 160 mm Hg. BPs were measured every 15 minutes during the initial 2 hours and every 60 minutes in the next 22 hours (a total of 30 measurements). The mean achieved SBP was defined as the mean of 30 SBPs, and associations between the mean achieved SBP and neurological deterioration (≥2 points' decrease in Glasgow Coma Score or ≥4 points' increase in National Institutes of Health Stroke Scale score), hematoma expansion (>33% increase), and unfavorable outcome (modified Rankin Scale score 4-6 at 3 months) were assessed with multivariate logistic regression analyses. RESULTS: Of the 211 patients (81 women, median age 65 [interquartile range, 58-74] years, and median initial National Institutes of Health Stroke Scale score 13 [8-17]) enrolled, 17 (8%) showed neurological deterioration, 36 (17%) showed hematoma expansion, and 87 (41%) had an unfavorable outcome. On multivariate regression analyses, mean achieved SBP was independently associated with neurological deterioration (odds ratio, 4.45; 95% confidence interval, 2.03-9.74 per 10 mm Hg increment), hematoma expansion (1.86; 1.09-3.16), and unfavorable outcome (2.03; 1.24-3.33) after adjusting for known predictive factors. CONCLUSIONS: High achieved SBP after standardized antihypertensive therapy in hyperacute intracerebral hemorrhage was independently associated with poor clinical outcomes. Aggressive antihypertensive treatment may ameliorate clinical outcomes.

DOI： 10.1161/STROKEAHA.113.001212

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND AND PURPOSE: Recent studies have shown that thrombolysis could decrease or eliminate ischaemic diffusion-weighted imaging lesions. However, the features of such diffusion-weighted imaging lesion reduction are not well known. AIMS: To clarify, the frequency of and factors associated with lesion reduction were investigated. METHODS: Patients given intravenous tissue plasminogen activator therapy within three-hours of onset were prospectively enrolled. Magnetic resonance imaging including diffusion-weighted imaging and magnetic resonance angiography was performed four times: on admission, just after intravenous tissue plasminogen activator, 24 h from intravenous tissue plasminogen activator, and seven-days after intravenous tissue plasminogen activator. The diffusion-weighted imaging lesion volume was measured by manual trace using National Institutes of Health imaging software. All patients were divided into three groups according to the early diffusion-weighted imaging lesion volume change from admission to just after intravenous tissue plasminogen activator: the lesion reduction group (>20% decrease); the lesion growth group (>20% increase); and the lesion unchanged group. RESULTS: In total, 105 patients [56 males, median age 77 (interquartile range 70-83) years, and National Institutes of Health Stroke Scale score 16 (10-22)] were enrolled. Early diffusion-weighted imaging lesion reduction was observed in seven (7%) patients. The decreased lesion increased subsequently. On multivariate analysis, the glucose level on admission (odds ratio 0·95, 95% confidence interval 0·91 to 0·99, P = 0·045) and early recanalization (odds ratio 15·7, 95% confidence interval 1·61 to 153, P = 0·018) were independently related to early lesion reduction. CONCLUSION: Early diffusion-weighted imaging lesion reduction was observed in 7% of patients treated with intravenous tissue plasminogen activator. The decreased lesion increased subsequently. Initial glucose level and early recanalization were independently associated with early diffusion-weighted imaging lesion reduction.

DOI： 10.1111/j.1747-4949.2012.00902.x

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記述言語：日本語   掲載種別：研究論文（学術雑誌）  

A 46-year-old man with a history of the left retinal central artery obstruction and old cerebral infarction in the right middle cerebral artery region presented with right total blindness due to the right retinal central artery occlusion accompanied by a cherry red spot. He had been found to have a giant, 17 mm-in-diameter aneurysm of the right internal carotid artery and a right vertebral arterial aneurysm. The intra-arterial thrombolysis was performed with urokinase injection for the right eye artery origin, and the right eyesight has improved. Cranial and pelvic angiography showed multiple stenosis and dilatation of external carotid and internal iliac arteries. The right superficial temporal artery biopsy revealed the arteritis with fibrinoid necrosis. He was diagnosed as having polyarteritis nodosa (PAN) by clinical course, angiography, and the superficial temporal artery biopsy. Several studies have reported that PAN had less intracranial aneurysm and the diameter of the aneurysm was less than 5 mm. Our case is the first report that PAN had giant aneurysm of 17 mm, diagnosed by temporal artery biopsy. The temporal artery biopsy should be considered to diagnose PAN.

DOI： 10.5692/clinicalneurol.53.452

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND AND PURPOSE: Our aim in this study was to investigate factors associated with paroxysmal atrial fibrillation (PAF) in acute stroke patients and to develop a risk score to predict the presence of PAF. METHODS: We retrospectively enrolled patients with acute ischemic stroke within 24h of onset between June 2006 and April 2008. Patients with sustained AF were excluded. Patients were divided into two groups according to the presence of PAF: the PAF group or the non-PAF group. The clinical factors associated with PAF were investigated. Furthermore, we devised a new risk score to predict the presence of PAF. RESULTS: There were 215 patients enrolled. The PAF group had 32 (14.9%) patients. Multivariate logistic regression analysis demonstrated that NIHSS score≥8 (OR, 4.2; 1.38-12.88), left atrial size≥3.8 cm (OR, 4.8; 1.65-13.66), mitral valvular disease (OR, 7.5; 2.17-25.90), and plasma BNP level≥144 pg/ml (OR, 12.8; 4.12-40.00) were independent factors associated with PAF. We developed a risk score from these variables (total score 0 to 5): NIHSS score≥8 (1 point); left atrial size≥3.8 cm (1 point); mitral valvular disease (1 point); and BNP level≥144 pg/ml (2 points). The frequency of PAF was 0% with a score of 0, 4% with a score of 1, 14% with a score of 2, 26% with a score of 3, 50% with a score of 4 and 100% with a score of 5 CONCLUSION: Our simple score can predict the presence of PAF during hospitalization in acute ischemic stroke.

DOI： 10.1016/j.jns.2013.02.025

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：ELSEVIER SCIENCE BV  

BACKGROUND: We aimed to devise a scale comprising a simple multiplication of initial National Institutes of Health Stroke Scale (NIHSS) score and onset-to-treatment time (OTT) as a scale for predicting outcomes after recombinant tissue plasminogen activator (rt-PA) therapy. METHODS: Data from rt-PA patients in 10 stroke centers in Japan were investigated. NIHSS-time score was calculated as initial NIHSS score×OTT. RESULTS: Subjects comprised 526 patients. Median NIHSS score was 12 (7-18), and median OTT was 2.42 h (2.00-2.75 h). Median NIHSS-time score was 27.7 (16.9-41.7). Good (modified Rankin Scale [mRS] 0-1) and poor (mRS 4-6) outcome rates at 3months for patients with NIHSS-time scores ≤ 10 were 71.1% and 7.8%, compared to 54.7% and 16.5% for scores >10 and ≤ 20, 38.9% and 31.9% for scores >20 and ≤ 30, 25.0% and 44.6% for scores >30 and ≤ 40, and 17.4% and 61.8% for scores >40, respectively. Cut-off NIHSS-time scores to predict good and poor outcomes with 50% probability were defined as 20 and 40, respectively. Multivariate logistic regression analysis revealed NIHSS-time score as an independent predictor of good (odds ratio [OR], 0.587; 95% confidence interval [CI], 0.422-0.818, p=0.002) and poor (OR, 1.756; 95%CI, 1.227-2.514, p=0.002) outcomes after adjusting for age, sex, NIHSS score, OTT, Alberta Stroke Program Early CT Score, internal carotid artery occlusion, and glucose level. CONCLUSIONS: NIHSS-time score predicts clinical outcomes in rt-PA patients.

DOI： 10.1016/j.jns.2013.01.029

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：WILEY-BLACKWELL  

A diffusion-weighted imaging (DWI) lesion changed dramatically in a hyperacute stroke case treated with intravenous tissue-plasminogen activator (IV t-PA). The initial hyperintense lesion on DWI disappeared completely immediately after IV t-PA treatment without improvement of neurological symptoms. However, the lesion reappeared 24 hours later. Successful thrombolysis can resolve DWI lesions but does not always improve the neurological symptoms.

DOI： 10.1111/j.1552-6569.2011.00635.x

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：WILEY-BLACKWELL  

BACKGROUND We investigated how many contrast-transcranial Doppler (c-TCD) examinations should be performed on different days in patients with acute stroke. METHODS Consecutive acute stroke patients within 24 hours of onset were enrolled. Presence of RLS was examined using c-TCD examinations on days 1, 7, and 14. Each c-TCD examination used one test without Valsalva maneuver (VM) and three tests with VM. Patients were diagnosed with RLS when TCD detected 1 microembolic signal on 1 c-TCD examination on any of the days 1, 7, or 14. RESULTS One hundred seventy patients (105 men [62%]; median age, 74 [IQR, 6681] years) were enrolled. RLS was diagnosed in 45 patients (26%). RLS was identified on day 1 in 30 patients (18%), on day 7 in 28 patients (16%), and on day 14 in 23 patients (14%; P= .143). Detection rate of RLS by combining day 1 and 7 examinations was significantly higher than that of day 1 alone (25% vs 18%, P &lt; .001). However, the rate did not increase when results of day 14 were added (25% vs 26%, P= .250). CONCLUSIONS c-TCD examinations should be performed on at least two different days to assess the prevalence of RLS.

DOI： 10.1111/j.1552-6569.2011.00660.x

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND AND PURPOSE: The present study determines associations between early blood pressure (BP) variability and stroke outcomes after intravenous thrombolysis. METHODS: In 527 stroke patients receiving intravenous alteplase (0.6 mg/kg), BP was measured 8 times within the first 25 hours. BP variability was determined as ΔBP (maximum-minimum), standard deviation (SD), coefficient of variation, and successive variation. RESULTS: The systolic BP course was lower among patients with modified Rankin Scale (mRS) 0 to 1 than those without (P<0.001). Most of systolic BP variability profiles were significantly associated with outcomes. Adjusted odds ratios (95% confidence interval) per 10 mm Hg (or 10% for coefficient of variation) on symptomatic intracerebral hemorrhage were as follows: ΔBP, 1.33 (1.08-1.66); SD, 2.52 (1.26-5.12); coefficient of variation, 3.15 (1.12-8.84); and successive variation, 1.82 (1.04-3.10). The respective values were 0.88 (0.77-0.99), 0.73 (0.48-1.09), 0.77 (0.43-1.34), and 0.76 (0.56-1.03) for 3-month mRS 0 to 1; and 1.40 (1.14-1.75), 2.85 (1.47-5.65), 4.67 (1.78-12.6), and 1.99 (1.20-3.25) for death. Initial BP values before thrombolysis were not associated with any outcomes. CONCLUSIONS: Early systolic BP variability was positively associated with symptomatic intracerebral hemorrhage and death after intravenous thrombolysis.

DOI： 10.1161/STROKEAHA.112.681007

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記述言語：英語   出版者・発行元：LIPPINCOTT WILLIAMS & WILKINS  

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：WILEY-BLACKWELL  

Background and purpose: Sleep-disordered breathing (SDB) is a risk factor for cerebrovascular disease. We investigated the frequency of SDB in Japanese patients with acute ischaemic stroke and transient ischaemic attack (TIA), as well as factors associated with SDB severity.
Methods: Between April 2010 and March 2011, we prospectively enrolled patients with ischaemic stroke and TIA within 24 h of onset to participate in a sleep study within 7 days of admission. We defined SDB as a respiratory disturbance index (RDI) (number of apnoeas or hypopnoeas per hour) of &gt;= 5. Patients were assigned to groups based on RDI values of &gt;= 30 (severe) and &lt;30 (absent or not severe). The frequency of SDB and factors associated with severity were investigated using multivariate regression analysis.
Results: We enrolled 150 patients amongst whom 126 (84%) had SDB. The frequencies of SDB were 21 (75%) patients with TIA, 105 (86%) with ischaemic stroke, 8/10 (80%) with large artery atherosclerosis, 14/14 (100%) with small vessel occlusion, 37/41 (90%) with cardioembolism and 46/57 (81%) with other causes of stroke/undetermined. Severe SDB was evident in 44 (29%) patients. The frequency of males (75% vs. 56%, P = 0.027), atrial fibrillation (AF) (39% vs. 23%, P = 0.045), higher body mass index (23.8 +/- 3.8 vs. 22.3 +/- 3.8, P = 0.043) and a larger neck circumference (37.8 +/- 4.3 vs. 35.8 +/- 4.2, P = 0.012) was significantly higher in the group with severe SDB. Multivariate regression analysis found that AF (OR 2.4; 95% CI 1.079-5.836, P = 0.0359) was independently associated with severe SDB.
Conclusion: Most Japanese patients with acute ischaemic stroke and TIA had SDB, and AF was associated with SDB.

DOI： 10.1111/j.1468-1331.2012.03837.x

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND AND PURPOSE - : In patients with middle cerebral artery trunk occlusion we investigated whether the diffusion-weighted imaging- the Alberta Stroke Program Early Computed Tomography Score (DWI-ASPECTS) predicts short-term neurological recovery after intravenous recombinant tissue plasminogen activator administration, and investigated how DWI-ASPECTS relates to clinical outcome. METHODS - : Dramatic recovery was defined as a ≥10-point reduction or a total National Institutes of Health Stroke Scale score of 0 to 1 at 24 hours and 7 days. Early recanalization was defined as recanalization within 1 hours after intravenous recombinant tissue plasminogen activator. Favorable outcome at 3 months was defined as a modified Rankin Scale score of 0 to 2. RESULTS - : Sixty-six patients (median age [interquartile], 79 [70-85] years, male
34 [52%]) were enrolled. DWI-ASPECTS was 6 (5-9). Dramatic recovery was seen in 16 (24%) and 26 (39%) patients at 24 hours and on day 7, respectively. Early recanalization occurred in 22 (33%) patients. DWI-ASPECTS ≥7 was an independent predictor of dramatic recovery at 24 hours (odds ratio, 100.85
95% confidence interval, 4.29-2371.40
P=0.004) and 7 days (odds ratio, 14.15
95% confidence interval, 2.21-90.48
P=0.005). Although the favorable outcome rate was not significantly different between patients with DWI-ASPECTS ≥7 with and without early recanalization (60% versus 31%
P=0.228), it was statistically more frequent in patients with DWI-ASPECTS &lt
7 with early recanalization than those without early recanalization (38% versus 0%
P=0.017). CONCLUSIONS - : DWI-ASPECTS predicted short-term recovery in patients with middle cerebral artery trunk occlusion receiving intravenous recombinant tissue plasminogen activator. In patients with lower DWI-ASPECTS, there may still be benefit from early recanalization. © 2013 American Heart Association, Inc.

DOI： 10.1161/STROKEAHA.112.675470

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記述言語：英語   出版者・発行元：LIPPINCOTT WILLIAMS & WILKINS  

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：KARGER  

Background and Purpose: Our previous retrospective study demonstrated that a brain natriuretic peptide (BNP) level of &gt;140 pg/ml on admission was useful to distinguish cardioembolism (CE) from non-CE. The aim of the present study was to prospectively investigate the utility of this predefined threshold. Method: Two hundred and twenty-one consecutive patients were prospectively enrolled. On admission, the BNP levels of the patients were measured and classified according to low BNP (&lt;= 140.0 pg/ml) or high BNP (&gt;140.0 pg/ml) levels. Final diagnosis of stroke subtype on discharge was made using the TOAST criteria. Measured parameters included the sensitivity, specificity, positive predictive value, and negative predictive value for CE in the high BNP group. Results: There were 81 patients in the high BNP group and 140 patients in the low BNP group. A total of 76 (34.4%) patients were diagnosed with CE, including 59 (72.8%) patients in the high BNP group and 17 (12.1%) patients in the low BNP group (p &lt; 0.001). A BNP level &gt;140.0 pg/ml corresponded to a sensitivity of 77.6%, specificity of 84.8%, positive predictive value of 72.8%, and negative predictive value of 87.9% for a diagnosis of CE. Conclusion: A BNP level of &gt;140.0 pg/ml on admission in patients with acute ischemic stroke is a strong biochemical predictor for CE. Copyright (C) 2013 S. Karger AG, Basel

DOI： 10.1159/000342887

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：KARGER  

Background: It is unknown whether the clinical features and outcomes of intracerebral hemorrhage (ICH) patients who undergo maintenance hemodialysis (HD) at the time of ICH are similar to those of general ICH patients. Methods: We retrospectively examined the medical records of ICH patients admitted to the Stroke Center of Kawasaki Medical School Hospital within 7 days of ICH onset between April 2004 and June 2011. Patients were classed as HD or non-HD, and clinical characteristics were compared between the two groups. ICH volume was measured on admission CT and follow-up CT scan (&lt;24 h after admission). Hematoma enlargement was defined as a hematoma that increased by more than 33% of its initial volume. Early death was defined as all-cause death within 14 days of ICH onset. The factors associated with early death were determined using multivariate logistic regression analysis. Results: Five hundred and seven patients (320 males; 69.0 years old, interquartile range 59.0-79.0) were enrolled in the study. Thirty-six (7.2%) were receiving maintenance HD at the time of ICH and formed the HD group, and the remaining 471 patients formed the non-HD group. Use of antithrombotic agents prior to ICH was more common in the HD group than in the non-HD group (41.7 vs. 21.9%; p = 0.012). Brainstem (30.6 vs. 11.3%; p = 0.003) and lobar (19.4 vs. 6.6%; p = 0.013) hematoma locations were more common in the HD group than in the non-HD group. Enlargement of ICH volume was more common in the HD group than in the non-HD group (25.8 vs. 10.2%; p = 0.015). Early death was more common in the HD group than in the non-HD group (33.3 vs. 9.3%; p &lt; 0.001). On the multivariate logistic regression analysis adjusted for age, sex and renal dysfunction, National Institutes of Health Stroke Scale score &gt;20 [odds ratio (OR) 27.40, 95% confidence interval (CI) 9.69-77.44; p &lt; 0.001], ICH volume &gt;30 ml (OR 9.53, 95% CI 3.82-23.77; p &lt; 0.001), HD (OR 6.42, 95% CI 1.39-29.76; p = 0.017), the use of antithrombotic agents (OR 3.04, 95% CI 1.22-7.56; p = 0.017) and glucose &gt;150 mg/dl (OR 2.51, 95% CI 1.01-6.26; p = 0.047) were independent factors associated with early death. Conclusion: Maintenance HD is independently associated with early death in ICH patients. Copyright (c) 2013 S. Karger AG, Basel

DOI： 10.1159/000351504

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記述言語：英語   出版者・発行元：KARGER  

DOI： 10.1159/000353284

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：KARGER  

Background and Purpose: We investigated whether brain natriuretic peptide (BNP) can serve as a biological marker of long-term mortality in ischemic stroke survivors. Methods: Consecutive patients with ischennic stroke within 24 h of onset from April 2007 to December 2010 were prospectively enrolled, and admission plasma BNP levels were measured. Survivors were followed up until 1 year after stroke onset. Patients were divided into two groups: the deceased group and the surviving group. The factors associated with long-term mortality were investigated by multiple logistic regression analysis. Results:A total of 736 patients who were alive at hospital discharge were included; 130 (17.7%) patients died. On multivariate analysis, age &gt;75 years (odds ratio, OR, 2.83; 95% CI, 1.74-4.60, p = 0.0001), dialysis-dependent chronic renal failure (OR, 5.99; 95% CI, 2.18-16.47, p = 0.0005), modified Rankin Scale score &gt;3 at discharge (OR, 4.41; 95% CI, 2.76-7.05, p &lt;0.0001), and plasma BNP &gt;100.0 pg/ml (OR, 3.94; 95% CI, 2.31-6.73, p &lt; 0.0001) were found to be independently associated with long-term mortality. We developed a risk score from 4 variables (each variable: 1 point, total score: 0-4 points). The mortality rates were 2% with a score of 0, 9% with a score of 1, 27% with a score of 2 and 50% with a score Conclusions: The risk score, composed of clinical parameters and BNP, may predict long-term mortality in ischemic stroke survivors. Copyright 2013 (C) S. Karger AG, Basel

DOI： 10.1159/000351777

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：LIPPINCOTT WILLIAMS & WILKINS  

OBJECTIVE: Optimal blood pressure (BP) control in acute intracerebral hemorrhage (ICH) remains controversial. We determined the effects of SBP lowering to 160 mmHg or more using intravenous nicardipine for acute ICH patients. METHODS: This is a prospective, multicenter, observational study conducted in Japan, with the lack of control groups. Patients with supratentorial ICH within 3 h of onset, admission SBP 180 mmHg or more, Glasgow Coma Scale (GCS) 5 or more, and hematoma volume less than 60 ml were initially treated with intravenous nicardipine to maintain SBP between 120 and 160 mmHg with 24-h frequent BP monitoring. The primary endpoints were neurological deterioration within 72 h [GCS decrement ≥ 2 points or National Institutes of Health Stroke Scale (NIHSS) increment ≥ 4 points; estimated 90% confidence interval (CI) on the basis of previous studies: 15.2-25.9%] and serious adverse effects (SAE) to stopping intravenous nicardipine within 24 h (1.8-8.9%). The secondary endpoints included hematoma expansion more than 33% at 24 h (17.1-28.3%), modified Rankin Scale (mRS) 4 or more (54.5-67.9%) and death at 3 months (6.0-13.5%). RESULTS: We enrolled 211 Japanese patients (81 women, 65.6 ± 12.0 years old). At baseline, BP was 201.8 ± 15.7/107.9 ± 15.0 mmHg. Median hematoma volume was 10.2 ml (interquartile range 5.6-19.2), and NIHSS score was 13 (8-17). Neurological deterioration was identified in 17 patients (8.1%), SAE in two (0.9%), hematoma expansion in 36 (17.1%), mRS 4 or more in 87 (41.2%), and death in four (1.9%). All the results were equal to or below the estimated lower 90% CI. CONCLUSION: SBP lowering to 160 mmHg or less using nicardipine appears to be well tolerated and feasible for acute ICH.

DOI： 10.1097/HJH.0b013e328359311b

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：NATURE PUBLISHING GROUP  

Cerebral microbleeds (CMBs) are recognized as a manifestation of arteriolosclerosis in cerebral small vessels. However, little is known regarding whether stroke patients with CMBs often have systemic atherosclerosis. The aim of the present study was to elucidate this issue using the cardio-ankle vascular index (CAVI), a new index of systemic atherosclerosis, in acute ischemic stroke patients. We prospectively studied 105 patients (71 males, median age=70.0 years) with acute ischemic stroke. All of the patients were examined using T2*-weighted gradient echo magnetic resonance imaging (MRI) to look for and assess the CMBs and using fluid-attenuated inversion recovery to evaluate white matter hyperintensity (WMH). We assigned the patients into CMB and non-CMB groups and compared the clinical characteristics of these groups. The factors associated with CMBs were investigated using multivariate logistic regression analysis. T2*-weighted gradient echo MRI revealed CMBs in 47 patients (44.8%) and no CMBs in 58 patients (55.2%). The CAVI was significantly higher in the CMBs group (10.5 vs. 8.6, P<0.001). In the multivariate logistic regression analysis, CAVI per one point increase (odds ratio (OR), 1.50; 95% confidence interval (CI), 1.12-2.00; P=0.006), advanced WMH (OR, 4.78; 95% CI, 1.55-14.74; P=0.006) and impaired kidney function (OR, 3.31; 95% CI, 1.16-9.81; P=0.031) were independent factors associated with the presence of CMBs. A high CAVI was independently associated with CMBs in patients with acute ischemic stroke. Our results indicated that ischemic stroke patients with CMBs may have cerebral arteriolosclerosis as well as systemic atherosclerosis.

DOI： 10.1038/hr.2012.84

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：ELSEVIER SCIENCE BV  

Background and purpose: The symptoms of about 30% of acute ischemic stroke patients progress, but the mechanism and predictors of the deterioration are not well known. The augmentation index (AIx), estimated with the arterial pulse waveform, is known to be pathophysiologically relevant to the pathogenesis of cardiovascular diseases. The aim of the present study was to investigate the prognostic value of the AIx for early symptom progression (ESP) in patients with acute ischemic stroke.
Methods: Acute ischemic stroke patients admitted to our stroke center within 24 h from onset were prospectively enrolled. The AIx was measured within 48 h from admission. ESP was defined as increase in the NIHSS score during 7 days from admission. All patients were divided into &gt;= 2 groups according to the ESP (the ESP group and the non-ESP group).
Results: A total of 147 patients (79 males, median age 74 [IQR 64-82] years, and NIHSS score 3 [1-7]) were enrolled. ESP was observed in 23 (16%) patients. There were no differences in clinical characteristics including the AIx between the two groups. However, when only cases with lacunar and atherothrombotic strokes were evaluated, the AIx was higher in the ESP group (37.0 [32.0-38.0]%) than in the non-ESP group (29.5 [21.8-33.3]%, p = 0.003). With the optimal cut-off value of &gt;36%, the AIx was independently associated with ESP (OR 37.3, 95% CI 1.71-811, p = 0.021).
Conclusion: The AIx level was independently related to ESP in patients with acute lacunar and atherothrombotic strokes. The AIx may have a potential to predict ESP in these patients. (C) 2012 Elsevier B.V. All rights reserved.

DOI： 10.1016/j.jns.2012.07.049

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC  

The aim of this study was to investigate the relation between brain natriuretic peptide (BNP) levels and the detection rate of new documented atrial fibrillation (AF) after ischemic stroke. Consecutive patients with ischemic stroke prospectively enrolled within 24 hours of onset. Patients with AF on admission electrocardiography or with histories of AF were excluded. The plasma BNP level was measured on admission, and the factors associated with new documented AF were investigated by multivariate logistic regression analysis. Furthermore, the detection rates of AF according to BNP level were evaluated. A total of 584 patients were enrolled. AF was detected in 40 patients (new AF group; 6.8%). The median BNP level of the new AF group was significantly higher than for the non-AF group (186.6 pg/ml [interquartile range 68.7 to 386.3] vs 35.2 pg/ml [interquartile range 15.9 to 80.1], p <0.0001). The cut-off level, sensitivity, and specificity of BNP levels to distinguish the new AF group from the non-AF group were 65.0 pg/ml, 80%, and 70%, respectively. Multivariate logistic regression analysis demonstrated that National Institutes of Health Stroke Scale score >7 (odds ratio 3.4, 95% confidence interval 1.685 to 7.006, p = 0.0007) and a plasma BNP level >65.0 pg/ml (odds ratio 6.8, 95% confidence interval 2.975 to 15.359, p <0.0001) were independently associated with new AF. The detection rates of AF according to BNP level were as follows: 2% of patients with <50 pg/ml, 4% of those with 50 to <100 pg/ml, 12% of those with 100 to <200 pg/ml, 26% of those with 200 to <400 pg/ml, and 38% of those with ≥400 pg/ml. In conclusion, BNP levels can predict new AF in patients with acute ischemic stroke. Elevated BNP levels result in an increase in the frequency of detection of new AF.

DOI： 10.1016/j.amjcard.2011.12.022

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：WILEY-BLACKWELL  

BACKGROUND We investigated whether combined transcranial Doppler (TCD) and magnetic resonance angiography (MRA) can diagnose significant stenosis (s-stenosis) of the siphon portion of the internal carotid artery (S-ICA) on digital subtraction angiography (DSA).
METHODS TCD criteria cut-off peak systolic blood-flow velocity of 75 cm/s or mean blood-flow velocity of 50 cm/s, with both values more than 30% higher than in the contralateral SICA. MRA criterion was defined as a = 50% signal reduction of the column width. Combined TCD and MRA criteria were fulfillment of both TCD and MRA criteria.
RESULTS Among 295 vessels, seven (2%) had s-stenosis on DSA. Using TCD criteria, 16 vessels (5%) were identified to have s-stenosis, of which six (38%) had s-stenosis on DSA (sensitivity, specificity, positive predictive value [PPV], and negative predictive value [NPV] were.86,.97,.38, and.99). Using MRA criteria, 17 (6%) vessels were s-stenosis, of which seven (41%) had s-stenosis on DSA. Sensitivity, specificity, and NPV were 1.00,.97, and 1.00; however, PPV was low (. 41). Combined TCD and MRA criteria identified six (2%) vessels as having s-stenosis, all were s-stenosis on DSA (PPV was 1.00).
CONCLUSION Combined TCD and MRA examinations have similar diagnostic power to DSA.

DOI： 10.1111/j.1552-6569.2010.00567.x

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：ELSEVIER IRELAND LTD  

Background: The aim of the present study was to investigate whether the prevalence of atrial fibrillation (AF) is associated with the level of glycated hemoglobin (HbA1c) in Japanese adults in Kurashiki-city.
Methods: Adult residents (&gt;= 40 years old) were examined twice, in 2006 and 2007. Electrocardiography was conducted to determine the presence of AF. After categorizing all participants into two groups (HbA1c &lt; 6.5% as low group and &gt;= 6.5% as high group), factors independently associated with the prevalence of AF were investigated in total cohort, low and high groups using multivariate logistic regression analysis.
Results: Of the total 52,448 participants (median age, 72 years; range, 65-78 years; 17,980 men), AF prevalence was 2.2% (1161/52,448). After classifying all participants by HbA1c level, the proportion of participants with AF was 2.2% (1073/49,498) in the low group and 3.0% (88/2950) in high group (p=0.005). AF was significantly associated with cardiac disease (OR, 5.78; 95% CI, 5.07-6.58; p&lt;0.001), elevating HbA1c (OR, 1.57; 95% CI, 1.33-1.84; p&lt;0.001), increasing age (OR, 1.40; 95% CI, 1.30-1.51; p&lt;0.001), and male sex (OR, 1.27; 95% CI, 1.10-1.47; p=0.001) in low group and was related to cardiac disease (OR, 4.85; 95% CI, 3.08-7.62; p&lt;0.001) and age (OR, 1.45; 95% CI, 1.09-1.93; p=0.010) in high group. After adjusted age, gender, vascular risk factors, cardiac disease, and eGFR, elevating HbA1c (OR, 1.18; 95% CI, 1.09-1.28; p&lt;0.001) was the factor in association with AF.
Conclusions: The presence of AF appears to be associated with the level of HbA1c, especially in patients with HbA1c &lt;6.5%. (C) 2010 Elsevier Ireland Ltd. All rights reserved.

DOI： 10.1016/j.ijcard.2010.10.039

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：ELSEVIER SCIENCE BV  

Background and purpose: The aim of the present study was to investigate whether administration of edaravone during t-PA infusion can enhance early recanalization in acute stroke patients.
Methods: This trial was undertaken as a multicenter, single blind, randomized, open-labeled study. Acute stroke patients with M1 or M2 occlusion within 3 h of onset were studied prospectively. The subjects were randomly allocated to edaravone (Edaravone group: when t-PA was intravenously infused, intravenous edaravone (30 mg) was started at the same time) and no edaravone (Non-Edaravone group). Early recanalization within 1 h after t-PA infusion and neurological recovery 24 h after t-PA infusion were compared between the two groups.
Results: 40 patients (23 men. 17 women; mean age, 76.4 +/- 8.2 years, median 79 years) were enrolled; 23 patients were assigned to the Edaravone group and 17 to the Non-Edaravone group. Early recanalization was more frequently observed in the Edaravone group than in the Non-Edaravone group (56.5% vs. 11.8%, P=0.0072). Eight patients who underwent endovascular therapy immediately after t-PA infusion were excluded, and neurological recovery was analyzed. Remarkable and good recoveries were more frequently observed in the Edaravone group than in the Non-Edaravone group (80.1% vs. 45.5%, P=0.0396).
Conclusion: Early recanalization and good neurological recovery were more frequently observed in the Edaravone group than in the Non-Edaravone group. These results demonstrate that administration of edaravone during t-PA infusion should enhance early recanalization in acute stroke patients. (C) 2011 Elsevier B.V. All rights reserved.

DOI： 10.1016/j.jns.2011.09.006

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：ELSEVIER SCIENCE BV  

Purpose: A nationwide survey was conducted regarding anticoagulant therapy in patients with acute intracerebral hemorrhage (ICH) on warfarin with nonvalvular atrial fibrillation (NVAF).
Methods: A questionnaire on standard therapeutic strategy for warfarin-related ICH in patients with NVAF was mailed to 416 institutes.
Results: A total of 329 physicians (79%) responded with a completed questionnaire. On admission, all respondents stopped warfarin medication and 94% normalized the international normalized ratio (INR) mainly by Vitamin K (63%), followed by fresh frozen plasma (20%), and prothrombin complex concentrate (10%). Afterwards, 91% of the respondents restarted anticoagulation and 3% used antiplatelet for prevention of thromboembolism, but the remaining 6% disagreed with restarting antithrombotic therapy. As contraindications for resuming anticoagulation, recurrent ICH (59%) and poor functional condition (59%) were often chosen. Of those who restarted anticoagulation, the timing was within 4 days in 7%, 5 to 7 days in 21%, 8 to 14 days in 25%, 15 to 28 days in 28% and 29 days or later in 18%. The major key finding on follow-up CT to restart anticoagulation was the absorption tendency of hematomas (47%). When restarting anticoagulation, 76% of the respondents used warfarin alone and 20% used either unfractionated heparin plus warfarin or heparin alone.
Conclusion: A large majority of respondents responsible for ICH management stopped oral warfarin medication and normalized INR on admission, and restarted anticoagulation after acute ICH in patients with NVAF. However, the strategies to normalize INR and to restart anticoagulant therapy varied greatly and depended on each individual physician's decision. (C) 2011 Elsevier B.V. All rights reserved.

DOI： 10.1016/j.jns.2011.08.017

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：WILEY-BLACKWELL  

PURPOSE
There have been some reports on right-to-left shunt as a cause of cryptogenic stroke. Although contrast transcranial Doppler (c-TCD) can detect RLS, an insufficient temporal window has occasionally restricted its applicability. Thus, we compared the rates of detecting RLS among temporal windows for the middle cerebral arteries (MCAs) and the orbital window for the internal carotid artery (ICA) on c-TCD.
METHODS
We used c-TCD to detect RLS in patients with suspected ischemic stroke. We enrolled patients who had both sufficient bilateral temporal windows for MCAs and a right orbital window for ICA and performed c-TCD using all three windows simultaneously.
RESULTS
We enrolled 106 consecutive patients and identified microembolic signals (MES) in 30 (28%) of them. Among these 30 patients, 15 had MES from all 3 windows. When these 30 patients were defined as being positive for RLS, the rates of detection were 67%, 73%, and 80% from the right temporal, left temporal, and right orbital windows, respectively (P = .795).
CONCLUSION
The right orbital window as well as the temporal window for c-TCD could detect RLS. Insonation from the orbital window should be useful for patients who lack temporal windows.

DOI： 10.1111/j.1552-6569.2010.00518.x

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：LIPPINCOTT WILLIAMS & WILKINS  

BACKGROUND AND PURPOSE: The purpose of this study was to determine the safety and efficacy of intravenous recombinant tissue-type plasminogen activator (0.6 mg/kg alteplase) within 3 hours of stroke onset in Japanese patients outside the indications in the European license. METHODS: Of the 600 patients who were treated with recombinant tissue-type plasminogen activator, 422 met the inclusion criteria of the European license (IN group) and 178 did not (OUT group). RESULTS: The OUT group was inversely associated with any intracerebral hemorrhage (adjusted OR, 0.50; 95% CI, 0.29-0.84), positively associated with an unfavorable outcome (2.48; 1.55-3.94) and mortality (2.04; 1.02-4.04), and not associated with symptomatic intracerebral hemorrhage (0.53; 0.11-1.79) or complete independency (0.65; 0.40-1.03) after multivariate adjustment. CONCLUSIONS: Functional and vital outcomes 3 months after low-dose recombinant tissue-type plasminogen activator in patients outside the European indications were less favorable compared with those included in the indications; however, the risk of intracerebral hemorrhage was not.

DOI： 10.1161/STROKEAHA.111.631176

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記述言語：英語   出版者・発行元：KARGER  

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：KARGER  

Background and Purpose: Vessel signs, such as the susceptibility vessel sign (SVS) on T2*-gradient echo imaging (T2*) and the hyperdense middle cerebral artery sign (HMCAS) on CT, are well-known markers of arterial occlusion. However, the relationship between the signs is not fully known. Methods: Patients suspected of having hyperacute (&lt;3 h from symptom onset) stroke were prospectively enrolled. MRI including T2* and MR angiography, and thin-section CT were performed on admission. The consistency between SVS and HMCAS were evaluated. Results: A total of 67 patients [38 males, median age: 76 (interquartile range: 67-82) years, median NIHSS score: 12 (4-21)] were enrolled. SVS was observed in 6 patients (9%), and HMCAS was present in 8 (12%). Sixteen patients (24%) had middle cerebral artery proximal (M1) occlusion on MR angiography. The presence or absence of SVS was highly consistent with that of HMCAS when all cases were evaluated (kappa = 0.841), as well as when only patients with M1 occlusion were assessed (kappa = 0.750). Conclusion: SVS and HMCAS were highly consistent with each other in suspected hyperacute stroke patients. SVS and HMCAS may represent the same thrombus. Copyright (C) 2012 S. Karger AG, Basel

DOI： 10.1159/000338308

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：KARGER  

BACKGROUND: The initial 24 h after thrombolysis are critical for patients' conditions, and continuous neurological assessment and blood pressure measurement are required during this time. The goal of this study was to identify the clinical factors associated with early neurological deterioration (END) within 24 h of stroke patients receiving intravenous recombinant tissue plasminogen activator (rt-PA) therapy and to clarify the effect of END on 3-month outcomes. METHODS: A retrospective, multicenter, observational study was conducted in 10 stroke centers in Japan. A total of 566 consecutive stroke patients [211 women, 72 ± 12 years old, the median initial NIH Stroke Scale (NIHSS) score of 13] treated with intravenous rt-PA (0.6 mg/kg alteplase) was studied. END was defined as a 4-point or greater increase in the NIHSS score at 24 h from the NIHSS score just before thrombolysis. RESULTS: END was present in 56 patients (9.9%, 18 women, 72 ± 10 years old) and was independently associated with higher blood glucose [odds ratio (OR) 1.17, 95% confidence intervals (CI) 1.07-1.28 per 1 mmol/l increase, p < 0.001], lower initial NIHSS score (OR 0.92, 95% CI 0.87-0.97 per 1-point increase, p = 0.002), and internal carotid artery (ICA) occlusion (OR 5.36, 95% CI 2.60-11.09, p < 0.001) on multivariate analysis. Symptomatic intracranial hemorrhage within the initial 36 h from thrombolysis was more common in patients with END than in the other patients (per NINDS/Cochrane protocol, OR 10.75, 95% CI 4.33-26.85, p < 0.001, and per SITS-MOST protocol, OR 12.90, 95% CI 2.76-67.41, p = 0.002). At 3 months, no patients with END had a modified Rankin Scale (mRS) score of 0-1. END was independently associated with death and dependency (mRS 3-6, OR 20.44, 95% CI 6.96-76.93, p < 0.001), as well as death (OR 19.43, 95% CI 7.75-51.44, p < 0.001), at 3 months. CONCLUSIONS: Hyperglycemia, lower baseline NIHSS score, and ICA occlusion were independently associated with END after rt-PA therapy. END was independently associated with poor 3-month stroke outcome after rt-PA therapy.

DOI： 10.1159/000339759

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